Multiple Sclerosis and Human Enhancement

Multiple sclerosis is a disease that raises a lot of interesting questions for people interested in biogerontology, human enhancement, and even cryonics. It raises questions about immunosenescence and draws attention to possible immune improvements for biological human enhancement. Biotechnologies to induce myelin repair may even be useful for the repair of cryopreserved brains. Before I discuss multiple sclerosis from these perspectives, let us take a closer look at this medical condition.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that results in axonal degeneration in the brain and spinal cord. In simple terms, multiple sclerosis is a disease wherein the body’s immune system attacks and damages the myelin sheath, the fatty tissue that surrounds axons in the central nervous system. The myelin sheath is important because it facilitates the conduction of electrical signals along neural pathways. Like electrical wires, neuronal axons require insulation to ensure that they are able to transmit a signal accurately and at high speeds. It is these millions of nerves that carry messages from the brain to other parts of the body and vice versa.

More specifically, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining the myelin sheath. This results in a thinning or complete loss of myelin (i.e., demyelination) and, as the disease advances, the breakdown of the axons of neurons. A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell’s myelin sheath. Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.

The name multiple sclerosis refers to the scars (sclerae—better known as plaques or lesions) that form in the nervous system. These scars most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord or white matter tracts close to the lateral ventricles of the brain. The peripheral nervous system is rarely involved. These lesions are the origin of the symptoms during an MS “attack.”

In addition to immune-mediated loss of myelin, which is thought to be carried out by T lymphocytes, B lymphocytes, and macrophages, another characteristic feature of MS is inflammation caused by a class of white blood cells called T cells, a kind of lymphocyte that plays an important role in the body’s defenses. In MS, T cells enter the brain via disruptions in the blood-brain barrier. The T cells recognize myelin as foreign and attack it, which is why these cells are also called “autoreactive lymphocytes.”

The attack of myelin starts inflammatory processes which trigger other immune cells and the release of soluble factors like cytokines and antibodies. Further breakdown of the blood–brain barrier in turn causes a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins. These inflammatory factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.

Because multiple sclerosis is not selective for specific neurons, and can progress through the brain and spinal cord at random, each patient’s symptoms may vary considerably. When a patient experiences an “attack” of increased disease activity, the impairment of neuronal communication can manifest as a broad spectrum of symptoms affecting sensory processing, locomotion, and cognition.

Some of the most common symptoms include: numbness and/or tingling of the limbs, like pins and needles; extreme and constant fatigue; slurring or stuttering; dragging of feet; vision problems, especially blurred vision; loss of coordination; inability to walk without veering and bumping into things; weakness; tremors; pain, especially in the legs; dizziness; and insomnia. There are many other symptoms, as well, such as loss of bowel or bladder control, the inability to process thoughts (which leads to confusion), and passing out. Some MS patients lose their vision and many lose their ability to walk. The symptoms are not necessarily the same for all patients and, in fact, an individual MS patient does not always have the same symptoms from day to day or even from minute to minute.

One of the most prevalent symptoms of MS is extreme and chronic fatigue. Assessment of fatigue in MS is difficult because it may be multifactorial, caused by immunologic abnormalities as well as other conditions that contribute to fatigue such as depression and disordered sleep (Braley and Chervin, 2010). Pharmacologic treatments such as amantadine and modafinil have shown favorable results for subjective measures of fatigue. Both drugs are well tolerated and have a mild side-effect profile (Life Extension Foundation, 2013).

It is estimated that multiple sclerosis affects approximately 85 out of every 100,000 people (Apatoff, 2002). The number of known patients is about 400,000 in the United States and about 2.5 million worldwide (Braley & Chervin, 2010). In recent years, there has been an increase of identified multiple sclerosis patients with about 50 percent more women reporting the disease. Indeed, between two and three times as many women have MS than men. Most patients are diagnosed between the ages of 20 and 50 but MS can strike at any age (National Multiple Sclerosis Society, 2013).

Incidence of multiple sclerosis varies by geographic region and certain demographic groups (Apatoff, 2002; Midgard, 2001). There is evidence that worldwide distribution of MS may be linked to latitude (Midgard, 2001). In the U.S., for instance, there is a lower rate of MS in the South than in other regions (Apatoff, 2002). Data regarding race shows 54 percent of MS patients are white, 25 percent are black and 19 percent are classified as other (Apatoff, 2002).

There are four disease courses identified in MS:

Relapsing-Remitting: Patients have clearly defined acute attacks or flare-ups that are referred to as relapses. During the relapse, the patient experiences worsening of neurologic function—the body or mind will not function properly. The relapse is followed by either partial or total recovery, called remissions, when symptoms are alleviated. About 85 percent of MS patients fall into this category (National Multiple
Sclerosis Society, 2013).

Primary-Progressive: The disease slowly and consistently gets worse with no relapses or remissions. Progression of the disease occurs over time and the patient may experience temporary slight improvements of functioning. About 10 percent of MS patients fall into this category (National Multiple Sclerosis Society, 2013).

Secondary-Progressive: Patient appears to have relapsing-remitting MS, but after time the disease becomes steadily worse. There may or may not be plateaus, flareups, or remissions. About half the people originally diagnosed with relapsing remitting will move into this category within 10 years (National Multiple Sclerosis Society, 2013).

Progressive-Relapsing: Quick disease progression with few, if any, remissions. About 5 percent of MS patients fall into this category at diagnosis (National Multiple Sclerosis Society, 2003).

The cause(s) of multiple sclerosis remain unknown although research suggests that both genetic and environmental factors contribute to the development of the disease (National Multiple Sclerosis Society, 2013; Compston and Coles, 2002). The current prevailing theory is that MS is a complex multifactorial disease based on a genetic susceptibility but requiring an environmental trigger, and which causes tissue damage through inflammatory/ immune mechanisms. Widely varying environmental factors have been found to be associated with the disease, ranging from infectious agents to Vitamin D deficiency and smoking. The debate these days revolves primarily around whether immune pathogenesis is primary, or acts secondarily to some other trigger (Braley & Chervin, 2010).

Risk factors for multiple sclerosis include genetics and family history, though it is believed that up to 75% of MS must be attributable to non-genetic or environmental factors. Infection is one of the more widely suspected non-genetic risk factors. A commonly held theory is that viruses involved in the development of autoimmune diseases could mimic the proteins found on nerves, making those nerves a target for antibodies. The potential roles of several viruses have been investigated including herpes simplex virus (HSV), rubella, measles, mumps, and Epstein Barr virus (EBV). The strongest correlation between a virus and MS exists with EBV—virtually 100% of patients who have MS are seropositive for EBV (the rate in the general public is about 90%)— but potential causality remains strongly debated (Ludwin and Jacobson, 2011).

It is important to keep in mind that infectious agents such as viruses may, in fact, have nothing to do with causing MS. The association of a virus with MS is based on increased antibody response and may be epiphenomenal of a dysregulated global immune response. “Proving” causality will require consistent molecular findings as well as consistent results from well-controlled clinical trials of virus-specific antiviral therapies (as yet to be developed). In the end, any theory concerning causality in MS should also account for the strong association with other environmental factors such as Vitamin D deficiency and smoking. Indeed, a landmark study found that, compared to those with the highest levels of vitamin D, those with the lowest blood levels were 62% more likely to develop MS. Additionally, a literature review evaluating more than 3000 MS cases and 45,000 controls indicates that smoking increases the risk of developing MS by approximately 50% (Life Extension Foundation, 2013).

Recently, researchers have pinpointed a specific toxin they believe may be responsible for the onset of MS. Epsilon toxin—a byproduct of the bacterium Clostridium perfringens—is able to permeate the blood brain barrier and has been demonstrated to kill oligodendrocytes and meningeal cells. Loss of oligodendrocytes and meningeal inflammation are both part of the MS disease process, and may be triggered by exposure to epsilon toxin.

The fact that females are more susceptible to inflammatory autoimmune diseases, including multiple sclerosis, points to the potential role of hormones in the etiology of multiple sclerosis. Interestingly, the course of disease is affected by the fluctuation of steroid hormones during the female menstrual cycle and female MS patients generally experience clinical improvements during pregnancy (Life Extension Foundation, 2013). Additionally, pregnancy appears to be protective against the development of MS. A study in 2012 demonstrated that women who have been pregnant two or more times had a significantly reduced risk of developing MS, while women who have had five or more pregnancies had one-twentieth the risk of developing MS compared to women who were never pregnant. (The increase in MS prevalence over the last few decades could reflect the fact that women are having fewer children.) A growing body of evidence supports the therapeutic potential of hormones (both testosterone and estrogens) in animal models of multiple sclerosis, but more research is needed to understand the pathways and mechanisms underlying the beneficial effects of sex hormones on MS pathology (Gold and Voskuhl, 2009).

No single test gives a definitive diagnosis for MS, and variable symptoms and disease course make early diagnosis a challenge. Most diagnoses are presumptive and are based on the clinical symptoms seen in an acute attack. Supporting evidence of these presumptions is then sought, usually from a combination of magnetic resonance imaging (MRI) of the brain, testing the cerebrospinal fluid (CSF) for antibodies, measuring the
efficiency of nerve impulse conduction, and monitoring symptoms over time.

As there is still much work to be done in understanding the nature of multiple sclerosis, a cure has yet to be discovered. Conventional medical treatment typically focuses on strategies to treat acute attacks, to slow the progression of the disease, and to treat symptoms. Corticosteriods such as methylprednisolone are the first line of defense against acute MS attacks and are administered in high doses to suppress the immune system and decrease the production of proinflammatory factors. Plasma exchange is also used to physically remove antibodies and proinflammatory factors from the blood.

The use of beta interferons is a longstanding MS treatment strategy, originally envisioned as an antiviral compound. Beta interferons reduce inflammation and slow disease progression, but the mechanism of action is poorly understood. Other immunosuppressant drugs such as Mitoxantrone and Fingolimod also slow disease progression, but are not used as first-line treatments due to their severe side effects. More recently, researchers at Oregon Health & Science University have noted that an antioxidant called MitoQ has been shown to significantly reverse symptoms in a mouse model of MS (Mao, Manczak, Shirendeb, and Reddy (2013).

Besides pharmacological treatments, MS patients may benefit from therapies (such as physical and speech therapy) and from an optimized nutritional protocol. Supplementation with Vitamin D, Omega-3 and -6 fatty acids, Vitamin E, lipoic acid, Vitamin b12, and Coenzyme Q10 appear to be of particular potential benefit (Life Extension Foundation, 2013). Until a definitive cause for MS can be defined and a cure developed, such strategies, including hormone therapy, offer possible ways to improve quality of life over the course of disease progression.

Unlike Alzheimer’s disease, there does not appear to be a Mendelian variant of MS that will invariably produce the disease in people who have the gene. A somewhat puzzling variable is that MS predominantly tends to occur between the ages of 20 and 50. This appears to exclude approaching MS as a form of immunosenescence. After all, if MS would be a function of the aging immune system, we would see progressively more cases of MS as people get older (or in AIDS patients), ultimately involving many very old people. More likely, MS is a non age-related form of dysfunction of the immune system that is triggered by environmental factors (such as a viral infection). While many discussions about the role of viruses in debilitating diseases like Alzheimer’s and MS still suffer from an incomplete understanding of cause and effect, it seems reasonable to conclude that enhancement of the human immune system can greatly reduce disease and improve the quality of life, even in healthy humans.

One potential treatment for MS is to induce remyelination (or inhibit processes that interfere with efficient remyelination). Stem cells can be administered to produce oligodendrocyte precursor cells to produce the oligodendrocyte glial cells that are responsible for remyelination of axons. While the myelin sheaths of these remyelated axons are not as thick as the myelin sheaths that are formed during development, remyelination can improve conduction velocity and prevent the destruction of axons. While the dominant repair strategies envisioned for cryonics involve molecular nanotechnologies that can build any biochemical structures that physical law permits, it is encouraging to know that specific stem cell therapies will be available to repair and restore myelin function in cryonics patients as damage to myelin should be expected as a result of (prolonged) ischemia and cryoprotectant toxicity.

An interesting possibility is that remyelination therapies may also be used for human enhancement if these therapies can be tweaked to improve conduction velocity in humans or to induce certain desirable physiological responses by varying the composition and strength of the myelin sheath in various parts of the central nervous system.


Apatoff, Brian R. (2002). MS on the rise in the US. Neurology Alert 20(7), 55(2).

Braley, Tiffany J., Chervin, Ronald D. (2010). Fatigue in Multiple Sclerosis: Mechanisms, evaluation, and treatment. Sleep 33(8), 1061-1067.

Compston, Alastair, and Coles, Alasdair (2002). The Lancet 359(9313), 1221.

Gold, Stefan M., and Voskuhl, Rhonda R. (2009). Estrogen and testosterone therapies in multiple sclerosis. Progress in Brain Research 175: 239-251.

Life Extension Foundation (2013). Multiple Sclerosis, in: Disease Prevention and Treatment, 5th edition, 947-956.

Ludwin, SK, and Jacobson, S. (2011). Epstein- Barr Virus and MS: Causality or association? The International MS Journal 17.2: 39-43.

Mao, Peizhong, Manczak, Maria, Shirendeb, Ulziibat P., and Reddy, P. Hemachandra (2013). MitoQ, a mitochondira-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Biochimica et Biophysica Acta Molecular Basis of Disease 1832(12): 2322- 2331.

Midgard, R. (2001). Epidemiology of multiple sclerosis: an overview. Journal of Neurology, Neurosurgery and Psychiatry 71(3), 422.

Originally published as an article (in the Cooler Minds Prevail series) in Cryonics magazine, February, 2014