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When Will There Ever Be a Cure for Multiple Sclerosis?

December 27. 2018. 6 mins read

When Montel Williams was first diagnosed with Multiple Sclerosis (MS) in 1999, he raged against the disease on Larry King Live. And for good reason – MS sucks. MS is a debilitating disease of the nervous system that causes a broad range of physical, mental, and even psychiatric symptoms. The major visible signs of MS are difficulty with muscle coordination, muscle weakness, and problems with vision. The overall effect is that people with MS have trouble getting out of bed because of fatigue, sometimes stumble and fall from numbness or muscle weakness, and painfully struggle to get through the day. There exists the stigma that patients with MS won’t be able to work long, productive careers. And before the availability of the ABC drugs (Avonex, Betaseron, and Copaxone) in the early 1990s, most MS sufferers lived challenging lives. Flare-ups could happen at any point, and symptoms could last for months at a time. The disease is inescapable because there is no known cure for MS.

The coveted gender ratio at a party.
The coveted gender ratio at a party. Credit: Biogen

The majority of patients receive a diagnosis between ages 20 and 50 years old. Two to three times more women are diagnosed compared to men. Major risk factors for MS include genetics, air quality, and even which region of the world you live in. Apparently, people who live farther away from the equator are more likely to have the disease, especially areas with a lot of Northern Europeans (so better start investing in that Ecuadorian real estate, MBAs).

The Science Behind Multiple Sclerosis

There are several competing theories behind the causes of MS, but really no one knows for sure. MS seems to begin with your autoimmune system initiating a biological Arab Spring and attacking the nervous system. Myelin, a fat-rich insulating coating that covers the nerve fibers like plastic around wires, starts to break down from the autoimmune attacks, leaving the nervous system exposed. Over time, the nervous system becomes damaged from the repeated attacks, which leads to nasty neurological symptoms when connections break down between the brain and the body.

Just like a frayed iPhone cord.
Just like a frayed iPhone cord. Credit: MS Research Australia

The causes of this physiological revolution are also many and ill-defined. Researchers report that a type of herpes virus called Epstein-Barr Virus (EBV) may trigger MS symptoms and is involved in other chronic diseases like the beloved kissing disease, mononucleosis (looks like cooties really do exist, boys and girls). The virus spends most of its time living inside the genome of our body without much fuss (90% of the human population is infected with EBV), but environmental and genetic triggers such as stress or physiological changes in the host’s body can cause the virus to replicate and spread. Viral particles start shedding from immune cells, which causes confusion and results in autoimmune attacks. The main culprit in this metabolic drama is the B-cell, an immune cell that is the main target of EBV infections. These cells can suddenly go haywire during this replication stage and turn on neighboring neuron cells.

In a time when retroviruses walked the Earth.
In a time when retroviruses walked the Earth. Credit: GeNeuro

The Challenges of a Cure

The big brains tackling MS say that the disease is a pain to cure. Why? MS is primarily an inflammatory disease that requires a wide range of treatments to both prevent or reduce the chronic inflammation that initiates the damage to the nervous system, and to also repair the preexisting damage already there for a full cure. Plus, diagnosis of the disease is a challenge because there are no foolproof specific tests for MS, which requires a differential diagnosis to rule out all other possible conditions, meaning damage will have already occurred to the nervous system before a diagnosis and follow-up treatment can stop it. On top of that, defining what a cure is for MS in the first place has been a question that’s bugged the medical and scientific community. Should researchers focus on halting the progression of the disease, reverse the neurological damage produced by the condition, or completely prevent MS outright? Unfortunately, the research isn’t quite there for the last option since, again, medical scientists still aren’t certain what causes MS in the first place. Drugs exist to halt some of the progress of MS and even reduce the neurological damage, but for many patients, chronic relapses and flare-ups will continue throughout their lifetime.

Investing 101 – Don’t let this happen to your stock. Credit: CNBC.com

The result has been a long string of failures for drug candidates. Last year, Australian biotech company Innate Immunotherapeutics (INNMF), which recently changed its name to Amplia Therapeutics, crashed on the stock market after its latest clinical trials for its lead drug, MIS416, failed to show clinically meaningful results. In the same year, Teva Pharmaceutical Industries (TEVA) and Active Biotech (ACTI.ST) published their latest results for the multinational CONCERTO Phase III trials for MS drug candidate laquinimod, which failed to significantly reduce MS relapses.

The Market Potential for Multiple Sclerosis

The National MS Society estimates that nearly one million people in the United States are living with MS, with 2.3 million suffering from MS worldwide. However, there is no known registry for MS patients, and the current numbers are only rough estimates. In a report by the American Journal of Managed Care, management of MS comes at a very high cost. Total lifetime costs per MS patient is estimated to be $4.1 million. Depending on the severity of symptoms, annual healthcare costs for MS can range from $30,000 to $100,000 per year. That comes out to an estimated global average of $150 billion per year. A cure for MS could make quite a chunk of change from that potential market.

The tropics never looked so good.
The tropics never looked so good. Credit: MultipleSclerosis.net

Below we highlight a few of the companies that are developing new cures and therapies with an eye toward that potentially lucrative market.

Antibodies Cures for MS

Click for company websiteFounded in 2017, Maryland-based startup Viela Bio is a clinical-stage biotechnology company that has raised $282.3 million in a Series A from Chinese and Singaporean investors to develop antibody treatments for MS. Viela Bio was spun out of Swiss pharmaceutical giant AstraZeneca Pharmaceuticals with lead candidate inebilizumab for MS. Currently in Phase II development, inebilizumab is a humanized antibody that kills B-cells, which are immune cells involved in the autoimmune attacks on the nervous system.

Click for company websiteGeNeuro (GNRO.PA) is a Swiss biotechnology company that raised $37.6 million at IPO to design antibody treatments for MS, beginning with GNbAC1. GNbAC1 binds to a protein that can trigger the immune response and is produced by a retrovirus that may be involved in the development of MS.

GnbAC1 mode of action.
GnbAC1 mode of action. Credit: GeNeuro

The drug is currently progressing through Phase IIb clinical trials with 260 patients in partnership with French-owned pharmaceutical company Servier Laboratories.

Immunotherapy Cures for MS

Click for company websiteFounded in 2012, Atara Biotherapeutics (ATRA) is a biotechnology company based in San Francisco that has raised $59.3 million working on immunotherapy treatments for autoimmune diseases. Immunotherapy has proven to be a game-changer for cancer treatment in some cases, so maybe the same will be true for MS. The company is currently developing an off-the-shelf T-cell immunotherapy product called ATA190, which reprograms T-cells in the body to attack and kill B-cells infected with EBV, since EBV is believed to be a trigger involved in the progression of MS.

Atara Biotherapeutics has two drugs in the pipeline.
Atara Biotherapeutics has two drugs in the pipeline. Credit: Atara Biotherapeutics

The immunotherapy treatment is currently progressing through Phase I clinical trials, with six out of 10 patients showing improvements under the treatment.

First-In-Class Pharmaceutical Cures for MS

Founded in 2009, Silicon Valley-based Bionure Farma is a late-pre-clinical startup that’s raised $6.5 million through a Series A funding round. Bionure is working on developing first-in-class agonists for Serum and Glucocorticoid-Regulated Kinases (SGKs), a set of cell signaling pathways involved in neurogenerative diseases. Their lead candidate, BN201, is a pharmaceutical agent that promotes repair and regeneration of nerve tissue through remyelination around nerve fibers. BN201 is currently in Phase I to determine its safety profile and tolerability.

Stem Cell Cures for MS

Click for company websiteFounded in 2012, Imstem is a Connecticut biotechnology startup with $1.1 million in funding to develop treatments using stem cell therapy. The lion’s share of Imstem’s funding came from a stem cell research grant through a program led by the state of Connecticut. The company is focused on researching human pluripotent stem cells for repairing neural tissue. The main Imstem therapeutic for treating MS is still under the pre-Investigational New Drug (IND) phase.

Conclusion

MS is a painful disease that has wreaked havoc on people’s lives and careers. At the moment, MS patients have to content themselves with conventional management strategies that include expensive pharmaceutical cocktails to reduce flare-ups and relapses. Companies are working hard to commercialize advanced technologies in the form of stem cell therapies, antibodies, and immunotherapies, among others. However, no one seems to be close to solving the mystery of the disease, which leads us to wonder: When will there ever be a cure for MS?

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