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this photo is a scenario drawn by me, the person needs help with something so my point is that they can use technology to get the answer

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Whenever a thought is captured to mind and you want to learn more about it I can search up the topic and find a whole bunch of articles about it. If I have a question that cannot be answered by my peers I can go on the web where a whole bunch of experts are and can be educated on what I am interested in!

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Technology can easily show us where we are in one second. It can also show us how to get to our special desired destinations!!

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We can connect instantaneously with individuals in our communities or around the world thanks to advances in technology. This invention not only keeps us linked, but it also has the potential to make our lives safer and healthier.

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Technology -- making a better future for us

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Technology -- making a better future for us

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People around the globe suffer from a myriad of rare diseases, many of which have no cure or limited treatment options. Many patients have been living without hope of a significant improvement in their quality of life, but for some, one new area of drug development is starting to change that.

Antisense therapy is a type of treatment that uses antisense oligonucleotides to target messenger RNA (mRNA). Ionis Pharmaceuticals ( IONS) is leading the charge in using antisense therapy to treat many rare diseases, and they are partnering with many other pharmaceutical companies of all sizes to advance this research.

One such disease is Duchenne muscular dystrophy, or DMD, which Australian biotech company Antisense Therapeutics is facing head-on. Although many people have heard of muscular dystrophy, most may not have heard of DMD, the most common type of muscular dystrophy.

However, even though DMD is the most common type, it is still rare. About 20,000 children are diagnosed with it globally every year, and DMD is estimated to affect about one in every 5,000 male births. DMD is a degenerative genetic disorder that causes progressive muscle wasting in boys, although girls can be carriers and experience very minor symptoms not requiring treatment.

It's clear that vast improvements in treatment for DMD patients are needed, and this is where antisense therapy comes in. Sarepta Therapeutics has three antisense-based DMD drugs on the market already, but so far, those available treatments are directed at treating less than one-third of the boys suffering from DMD.

Through Ionis' partnership with Australia-based Antisense Therapeutics, another potential therapy that could treat a significantly larger percentage of DMD patients is in late-stage clinical development. I sat down with Antisense CEO Mark Diamond to talk about how antisense therapies are changing the face of treatment for many diseases today, including Duchenne muscular dystrophy.
Q: What is antisense technology?
A: Antisense is what we call a platform technology in the pharmaceutical industry, which means antisense drugs can be designed to block disease-causing proteins in a broad range of disease settings while using the elements needed to create such new treatments relatively quickly and efficiently.

Antisense technology was a critical breakthrough in the approach to treating disease, as traditional drug discovery usually requires years to produce lead compounds. Antisense drugs also benefit from uniform methods of manufacture, formulation and administration .

We've licensed the antisense technology we're working with from Ionis Pharmaceuticals, the largest player in the world in antisense drug discovery and commercialization. We have worldwide, exclusive licenses for two drugs from Ionis, including the one we are developing for Duchenne muscular dystrophy.
Q: How can it be used to treat rare, hard-to-treat diseases?
A: As researchers uncovered massive amounts of genomic information, numerous proteins that cause disease were simultaneously discovered. By targeting these proteins using antisense technology, we can look to treat those diseases. Every cell in our bodies contains numerous structures and biochemicals made from proteins or through the action of proteins. The nucleus of the cell contains the genetic blueprint for the production and control of those structures and biochemicals, and the chromosomes contain about 30,000 genes, which together make up the human genome.

Every gene contains instructions for and control of the manufacturing of a unique protein. Some proteins form the structure of the cell, while others are enzymes that carry out the cell's functions or hormones that interact with the cell's surroundings.

Most pharmaceuticals currently in use interact directly with proteins, enhancing or inhibiting the action of a protein or mimicking its role, resulting in the targeted therapeutic effect, whereas antisense technology works a step earlier by blocking or inhibiting the production of the protein in the first instance. The pharmaceuticals currently on the market target about 500 different proteins in total, leaving huge opportunities for drug discovery and new therapies for applying antisense technology, although not every protein is a suitable target for therapeutic intervention.
Q: What are some examples of diseases currently being treated by antisense drugs?
A: Antisense drugs are being used in the treatment of Batten disease, spinal muscular atrophy and other lesser-known diseases. Trials are being conducted on antisense drugs to treat Alzheimer's disease, cystic fibrosis, diabetes, hepatitis B, hypertension, Parkinson's, prostate cancer, Huntington's disease, and many diseases most people have never heard of.
Q: How do antisense therapies compare with traditional pharmaceuticals?
A: The human genome has roughly 30,000 genes that can be transcribed into roughly 85,000 different messenger RNA, each of which is used within the cell as a template to synthesize different proteins. Conventional pharmaceuticals, also called small chemicals, peptides, or proteins like hormones and antibodies, which are large proteins, usually bind directly to the protein to treat a disease.

However, antisense drugs bind to the target protein's mRNA, inhibiting the production of the protein. The sequencing of the human genome enabled the design of antisense drugs without needing the complex, time-consuming analysis of the target protein's structure required by traditional pharmaceuticals.
Q: How do antisense drugs work?
A: Antisense technology has been in development for more than 20 years, but the concept was originally conceived in 1978. Antisense technology has been refined over the years since then. Antisense compounds are designed to bind specifically to their targeted mRNA and interfere with it. The targeted mRNA contains the instructions to produce the protein targeted by the antisense drug.

To create antisense drugs, chemically stabilized nucleotides are synthetically linked in short chains of about 12 to 30 nucleotides, referred to as oligonucleotides when they are linked together. Every antisense drug is designed with the correct genetic code to bind to a specific nucleotide sequence through its mRNA target, forming a short area of double strands.

The double-stranded region then inhibits the production of the targeted protein through various mechanisms, such as preventing the instructions from being read or causing the mRNA to be destroyed by an enzyme already in the cells.
Q: How safe are antisense drugs?
A: Antisense molecules are chemically modified pieces of DNA designed to inhibit the production of specific disease-causing proteins. As a platform technology, it can be applied to a broad range of diseases. As a result, the safety profile of these antisense drugs is fairly similar.

As we see Ionis drugs going through successful clinical development and onto the market, it gives us confidence around the safety profile of our drug because the basic chemistry is very similar, which drives the safety profile of the drug in humans. We can bank on the data that Ionis has developed around the technology as a helpful indicator of the safety profile of our drug.

Like all drugs, antisense drugs do have side effects, although they are generally predictable, usually only occur at high doses, and are well understood. Ionis and its partners have tested more than 6,000 patients in trials for antisense drugs.
Q: What drugs do you have in your pipeline at Antisense Therapeutics and how do they work?
A: Our lead drug is ATL1102, which we have shown to be active in patients with multiple sclerosis, and, more recently, Duchenne muscular dystrophy. Antisense drugs are usually designed to block or inhibit the production of a protein. ATL1102 is designed to block a protein called CD49d, which is a receptor on the surface of T cells.

This receptor allows the white blood cell to bind to the blood vessel walls and move through the blood vessel into the tissue that is the site of inflammation in MS and DMD. So in multiple sclerosis, you've got aberrant movement of lymphocytes into the brain, causing an inflammatory response. In Duchenne's, the inflammation is in the muscles, so the receptor on the surface of the lymphocytes allows the white blood cells to migrate from the blood into the affected tissues.

In MS patients, we were able to reduce the number of new inflammatory brain lesions, we believe by reducing the CD49d protein on the T cells and keeping certain of them from going into the brain and causing more damage. MS is an autoimmune disease, with the body making antibodies against the myelin protective coating of the nerve cells in the brain, which leads to the immune cells entering the brain and the associated breakdown of the myelin.

It's much the same approach for Duchenne patients, where we are looking to stop lymphocytes from going into the muscles of the boys to cause more damage. That's the way the drug is designed to work.

A study showing ATL1102 activity in MS patients was published in the peer-reviewed Journal of Neurology. We're expecting data on Duchenne's patients to be published soon in another scientific journal. We're waiting for the peer review process to be completed. However, we've already presented the data at scientific conferences.

We also own the rights to the drug ATL1103, which is designed to block the growth hormone receptor, reducing levels of the hormone insulin-like growth factor in the blood. It's a potential treatment for diseases related to excessive growth hormone action like acromegaly, diabetic retinopathy and diabetic nephropathy. ATL1103 has been undergoing clinical development as a treatment for acromegaly, which causes abnormal growth of the organs, face, hands and feet.
Q: One of your drugs is being investigated for use in long COVID isn't it?
A: We believe ATL1102 may have potential benefit in helping long COVID patients, particularly those with neurological symptoms. We are conducting the first study in the world to assess up to 7,000 plasma proteins in long COVID patients, looking for disease markers in the blood to identify treatments, including the potential to use ATL1102 in this condition. We expect the first results from our tests in the middle of this year.
Q: Your focus right now is on your treatment for DMD. What symptoms do the boys suffering from this disease have to deal with?
A: Common symptoms of Duchenne muscular dystrophy include delayed motor development, a progressive weakening of muscles, waddling gait, progressive enlargement of the heart, delayed speech and language development, and cognitive impairment.

One of the earliest life-altering symptoms in boys with DMD is weakening muscles in their legs, which confines them to a wheelchair. Over time, their arms start to weaken as well, leaving them unable to do basic things like feeding themselves.

The standard of care for Duchenne muscular dystrophy is corticosteroids to reduce inflammation in the muscles, but this treatment appears less effective in boys with more advanced DMD symptoms and is associated with significant side effects when used chronically as is required in DMD. Eventually, the doctor may suggest halting corticosteroid use because of these side effects and that it may stop helping.
Q: What can you tell us about your current clinical trials?
A: For Duchenne muscular dystrophy, we completed a successful Phase 2 clinical trial in Australia at the Royal Children's Hospital in Melbourne, which runs the biggest clinic in the southern hemisphere treating Duchenne's boys. We ran our study in those boys more advanced with the disease who have lost the ability to walk and require a wheelchair. In our study, we dosed the boys once weekly for six months via a subcutaneous injection.

The advantage of subcutaneous administration is that it provides the potential for convenient self administration via prefilled syringe. The study's primary endpoint was safety and tolerability. The study met its primary endpoint as ATL1102 was assessed as being well-tolerated with no serious side effects and no patient withdrawals.

We also monitored disease progression in these non-ambulant boys by measuring the muscle strength and function of their upper body by testing the function of their shoulders, elbows, and wrists. Once the boys lose the ability to walk, the next line of muscles adversely impacted by this genetic disorder are those of the upper limbs, which has a profound effect on the quality of life for the boys.

Initially, the boys have no real compromising of quality of life beyond using a wheelchair. They can still feed themselves, use a computer keyboard or phone, and use the toilet, but they lose these basic skills as the disease progresses and they lose their upper limb function and strength. Even when they're on a maintenance dose of corticosteroids, they still lose the muscle function of their upper limbs.

However, in our study, we saw stabilization in strength and function of the upper limbs of the boys who received our drug. At the end of six months, we saw mean improvements in strength and function compared to the baseline we measured before they started receiving the drug.

It was an exciting discovery. Typically, you see increasing levels of fat in the muscle as the muscle cells die and are replaced by fat cells. But when we looked at the muscles of the boys under an MRI, we saw that the level of fat in the muscles had stabilized and that there was an increase in lean muscle mass. It's our understanding that this has never been observed in Duchenne's boys being treated with corticosteroids.

We are well advanced in our planning for a Phase IIb/III trial which will be run in Europe, where we will be dosing the boys for 12 months at two different dose levels. We will use the once-weekly 25mg subcutaneous dose used in the Phase II study we ran at Royal Children's Hospital, but the European Medicines Agency has also approved the use of a higher 50mg dose.

There will also be a placebo arm in the trial in which the boys will be on the standard of care, which is corticosteroids, or on no therapy at all. In the European study, we will be assessing the performance of upper limb function as the primary efficacy endpoint to see if treatment with ATL1102 provides superior therapeutic outcomes to those on stand of care.

We're excited by the prospect of being able to go into a trial with a higher dose and assess boys over a longer period of time. We anticipate that those on the placebo will continue to experience losses in muscle strength and function over the 12 months. If we can show stabilization of function in the boys who receive our drug over the anticipated losses of those on the placebo and a good safety profile, it should be the basis for us moving forward with a marketing application with the EMA.

We expect to include 105 patients in the trial, with one-third on the placebo arm and one-third on each of the two dosing arms. It's exciting to think as we embark on the Phase IIb/III study in Europe that we have already shown benefits on upper limb function in our Phase II trial, as this will be the primary efficiency endpoint for the European study.
Q: Why did you choose to target Duchenne muscular dystrophy?
A: It was an interesting decision made by the company. We had already demonstrated that the drug had shown encouraging activity in multiple sclerosis patients. Then a seminal publication in 2015 on research conducted by Brazilian and French researchers reported that Duchenne's boys seemed to have elevated levels of white blood cells that had high numbers of CD49d receptors.

As mentioned earlier, CD49d is the therapeutic target of ATL1102. The researchers showed a statistically significant difference in the number of lymphocytes expressing high levels of CD49d in the Duchenne's boys versus a no-disease population. Non-ambulant boys had even more of these lymphocytes with high levels of CD49d receptors than those at an earlier stage of the disease.

At the time of this key publication I had on my board Bill Goolsbee the ex-chairman of Sarepta Therapeutics, a leading company in the treatment of Duchenne's. Bill was very excited by the observations in the paper and its validation of the target of ATL1102 and thereby the potential application of our drug in this disease setting.

We also knew about the benefits of developing therapeutics for orphan diseases, including gaining orphan drug designation. In the U.S. and Europe, this designation comes with incentives like tax credits for qualified clinical trials and the potential for seven years and ten years, respectively, of market exclusivity after approval. Drugs that treat rare diseases that affect fewer than 200,000 people in the U.S. or no more than five in 10,000 people in Europe are designated orphan drugs.

Most importantly, we saw an opportunity for a small company like ourselves to be able to take a program all the way through approval because, being a rare disease, it requires much smaller trials and therefore, less expensive development. By way of contrast a Phase III trial for MS, for example, would require almost 2,000 patients to be dosed for two years before a company could submit the drug for approval. That's well beyond the financial means of a small biotech company.
Q: What are some of the other treatments in use for DMD, and how does your treatment differ?
A: Already approved treatments for DMD in the U.S. include PTC Therapeutics' Emflaza and Sarepta Therapeutics' Amondys 45, Exondys 51 and Vyondys 53.

In the U.S., boys suffering from DMD really only have two treatment options: corticosteroids like prednisolone and Emflaza and the exon-skipping drugs marketed by Sarepta Therapeutics and NS Pharma. The corticosteroids display modest efficacy and are associated with significant safety issues when used chronically, as required in DMD. The exon-skipping drugs are restricted to boys with specific genetic mutations, so with the three drugs that Sarepta has approved, only about 30% of the market is being addressed, leaving a large percentage of boys suffering from DMD without an effective treatment.

All boys with DMD have muscle inflammation, and so we believe they could benefit from an improved immunomodulatory/ antiinflammatory drug like ATL1102. Importantly, all boys receiving exon-skipping therapy are also on their maintenance doses of corticosteroids, so we feel there could be an opportunity to use ATL1102 in combination with the exon-skipping drugs to potentially improve efficacy.

We are running animal studies to test this combination approach, and those results are due in the second half of this year. The exon-skipping drugs require a once-weekly infusion, which means the boys have to go to a treatment center for their therapy. ATL1102 is subcutaneously administered once a week in clinical trials, so if approved, we expect it to be available as a pre-filled syringe like insulin, offering patients and their parents the convenience of self-administration.

Finally, the exon-skipping therapy is expensive, averaging around US$750,000 per patient per year. We expect to have a significant cost-of-goods advantage over the exon-skipping drugs, which are also antisense drugs but use a different chemistry and are directed at a different target than ATL1102.

For eteplirsen, they are administering 30mg per kilogram per week as an IV infusion, so in a 50kg Duchenne boy, that is 1500mg per week, compared to the 25mg and 50mg per week fixed doses of ATL1102 we are using in our Phase IIb/III trial. So compared to our high dose of 50mg/week, they are administering 30 times as much drug.

As the cost of manufacturing oligonucleotides is fairly comparable across the different chemistries, this gives a significant opportunity to price ATL1102 competitively versus the exon-skipping drugs, making treatment for DMD more affordable. Additionally, combining ATL1102 with the exon-skipping drugs could result in better therapeutics and would increase the size of our addressable market for this disease if the drug trial shows a benefit to the combination.
**Antisense is a client of Quantum Media Group, LLC
The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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Technology has transformed life as we know it, and the classroom looks much different than it did 50—or even 10—years ago.