Multiple sclerosis: Are we close to a cure?
Researchers are uncovering many potential treatment routes for MS. Could they be close to a cure?
Multiple sclerosis (MS) is a potentially disabling disease that affects the brain and spinal cord. Around 400,000 people are living with MS in the United States and approximately 2.1 million individuals have the condition worldwide.
The exact mechanism that drives MS is not entirely understood. However, many researchers suggest that the condition is an autoimmune disease that attacks the myelin sheath – that is, the protective layer surrounding the nerves that help electrical signals to travel from the brain to the rest of the body – in the brain and spinal cord.
Over time, the disease can deteriorate or permanently damage the nerves. Symptoms tend to vary depending on the nerves affected and the damage caused. While some people may lose the ability to walk, others experience extended periods of remission.
Drugs recently approved by the FDA
At present, disease-modifying therapies (DMTs) are the best strategy to slow the course of MS. DMTs reduce the frequency and severity of relapses – or attacks and exacerbations – and the development of new lesions, and slow down the progression of disability.
Ocrelizumab is the latest MS drug approved by the FDA.
The number of available DMTs has increased rapidly in recent years, and there are now 15 of them approved by the U.S. Food and Drug Administration (FDA) for relapsing forms of MS, including relapsing-remitting MS (RRMS). One of these is also the first to be approved for use in primary progressive MS (PPMS), and the FDA has approved another for use in secondary progressive MS (SPMS).
The newest addition to the DMT repertoire is ocrelizumab (Ocrevus).
The FDA approved a groundbreaking new drug in 2017 for the treatment of relapsing MS. The drug is also the first approved to treat PPMS. Research conducted by a team of researchers has shown that ocrelizumab significantly reduces relapses in relapsing MS and slows the progression of symptoms in PPMS.
Ocrelizumab, as with many other MS treatments, is an immunosuppressant drug. While most drugs for MS target T cells, ocrelizumab targets a subset of B cells that are thought to play a role in the destruction of myelin.
Phase III clinical trials for RRMS indicated that compared with interferon beta-1a, ocrelizumab was able to reduce relapse rates by up to 47 percent, cut back disability by up to 43 percent, and decreased inflammatory lesions in the brain by 95 percent.
A phase III clinical trial for PPMS found that after 12 weeks of receiving ocrelizumab or a placebo, progression of disability was 39.3 percent in the placebo group compared with 32.9 percent in those receiving ocrelizumab. By 120 weeks of treatment, a timed 25-foot walk worsened performance by 55.1 percent for placebo versus 38.9 percent for the ocrelizumab group.
Patients receiving ocrelizumab also had fewer brain lesions and less loss of brain volume than the placebo group.
Latest innovations in the MS drug pipeline
The development of new medicines can take 10 to 15 years from testing in a laboratory to being commercially available. For every 10,000 compounds tested, fewer than one or two become licensed treatments, with many rejected on the grounds of their safety, quality, and efficacy.
Some therapies in their final phase of clinical trials are listed below. If the drugs prove effective in this phase, data from phases I through III are presented to the FDA for approval. Only 25 to 30 percent of drugs progress to the next stage following FDA approval.
Laquinimod is an experimental drug in phase III trials for relapsing MS, and phase II trials for PPMS. Laquinimod may prevent immune cells from reaching the brain. Investigations have indicated that Laquinimod has both anti-inflammatory and neuroprotective actions, and it may affect the levels of certain cytokines, which are substances secreted by immune cells, as well as diminish the immune cells that gain passage to the brain and spinal cord.
Phase III studies of Laquinimod have shown a 23 percent reduction in annual relapse rate compared with a placebo, a 33 percent decrease in disability progression, and a 44 percent reduction in brain volume loss.
The idea behind autologous hematopoietic stem cell transplantation (AHSCT) is to “reboot” the immune system in people with MS. Hematopoietic, or blood cell-producing, stems cells derived from the person’s own (autologous) blood or bone marrow are collected and stored.
AHSCT may stop MS disease progression for at least 5 years.
After chemotherapy drugs are used to deplete much of the immune system, the stored stem cells are then reintroduced to the body, and the new cells make their way to the bone marrow and gradually rebuild the immune system within 3 to 6 months.
Imperial College London in the United Kingdom recently published the long-term outcomes of AHSCT in people with relapsing MS. They revealed that AHSCT might halt the symptoms of the disease from progressing for 5 years in 46 percent of MS patients.
However, the treatment carries significant risk due to the involvement of aggressive chemotherapy, the researchers stress.
MD1003 (high-dose biotin) is being tested in phase III trials for primary and secondary progressive MS. The drug is a highly concentrated form of biotin – 10,000 times the recommended daily intake – that activates enzymes involved in cell growth and myelin production. High doses of biotin may promote myelin repair.
Investigators compared MD1003 with a placebo in primary and secondary progressive MS. They found that 13 percent of individuals in the MD1003 group improved in disability after 9 months compared with no improvement in the placebo group.
Siponimod is being developed for use in SPMS. The drug works by trapping T cells and B cells in the body’s lymph nodes, which prevents them from entering the brain and spinal cord and causing damage to myelin.
In a phase III trial, siponimod was found to lower the risk of disability progression by 21 percent at 3 months of treatment and 26 percent at 6 months compared with a placebo. The drug was also shown to reduce the number of relapses experienced and brain shrinkage, or atrophy.
Recent MS treatment research
MS treatment research is moving at a rapid pace. Recent study findings have highlighted new areas for investigation, potential causes that have opened up new targets for treatment, and novel therapies for tackling disease progression and symptoms.
According to research by the Aarhus University and Aarhus University Hospital, both in Denmark, the University of Southern Denmark, and the University Medical Center Hamburg-Eppendorf in Germany, while cognitive training helps to reduce the cognitive symptoms of MS, resistance training may protect the nervous system, and, as a result, slow down the progression of MS.
Training with weights may help to protect the nervous systems and slow MS progression.
Study findings showed that physical training relieved some MS symptoms, including mobility impairments and excessive fatigue.
“Among persons with MS, the brain shrinks markedly faster than normal,” said Prof. Ulrik Dalgas, of the Department of Public Health at Aarhus University. “Drugs can counter this development, but we saw a tendency that training further minimizes brain shrinkage in patients already receiving medication. In addition, we saw that several smaller brain areas actually started to grow in response to training.”
An over-the-counter antioxidant called lipoic acid may prove valuable in the treatment of SPMS, according to researchers from the Oregon Health & Science University in Portland.
Their study revealed a 68 percent improvement when using lipoic acid compared with a placebo in slowing the rate of whole brain atrophy. As a comparison, the recently approved ocrelizumab showed an 18 percent improvement over placebo in slowing the rate of whole brain atrophy in primary progressive forms of MS.
Researchers from the Mayo Clinic in Rochester, MN, have reported that a human gut microbe called Prevotella histicola suppressed MS in mice. It decreased the levels of pro-inflammatory cells and increased levels of cell types that fight disease, including T cells, dendritic cells, and a form of macrophage.
“This is an early discovery but an avenue that bears further study,” says Dr. Joseph Murray, a Mayo Clinic gastroenterologist. “If we can use the microbes already in the human body to treat human disease beyond the gut itself, we may be onto a new era of medicine. We are talking about bugs as drugs.”
Is a cure for MS imminent?
As yet, there is no cure for MS. However, we are at a pivotal moment wherein researchers are making significant progress and breakthrough solutions toward a world free of MS.
Results from early mouse studies have indicated paralysis reversal in MS, which may have treatment implications for humans in the future.
Today, more therapies for MS are in development than ever before, and the disease is being diagnosed at a quicker rate, enabling early treatment to slow disease activity.
There is greater awareness of all the associated symptoms of MS and how to manage them to improve life quality. Furthermore, scientists have identified risk factors that make individuals more susceptible to MS, which may potentially lead to new ways to prevent the disease.
Researchers are making headway in testing approaches that protect the nervous system from MS-related damage. These strategies include using therapies that are already approved by the FDA for use in other disorders. Clinical trials assessing novel approaches to treating all forms of MS are also under way.
In learning how the nervous system and cells are damaged in MS, scientists have used their findings to investigate therapies aimed at repairing myelin. In mouse models of MS, researchers have already developed experimental treatments that have resulted in reversing paralysis and partially restoring myelination and limb function.
Researchers are pursuing leads that show how exercise and rehabilitation improve several functions and may help to rebuild and rewire certain areas of the brain.
Studies have uncovered modifiable lifestyle factors, such as smoking, vitamin D levels, and obesity, which could possibly decrease the chances of MS for the next generation. What is more, research teams have identified gene variations that influence a person’s susceptibility to MS.
All these clues and evidence combined help researchers to understand the causes of MS, how to develop improved treatments, and how to prevent the disease. While there is still no definitive answer on how to cure MS, advances in research and potential treatment avenues may one day unlock the solution to a cure.