GH, IGF-1 and MS

I've recently had a scare, and asked various MS (Multiple Sclerosis) centres (it's common in my family but have been told it's rarely hereditary) for any info on the effects of GH in relation to MS. Only one gave me a link on research that has been carried out. Some of you may find it interesting, possibly useful.

Progress in Research > Research Highlights Winter/Spring 2004

Growth Factors: Nourishing Repair in MS

By Sara M. Bernstein

Growth factors are proteins that provide powerful signals to regulate the growth of cells during embryonic stages and guide their development into mature, working cells. Investigators are discovering that the work of these natural proteins doesn’t stop there: Growth factors have demonstrated remarkable effects on protecting against or repairing nervous system damage such as that which occurs in MS. These proteins may hold potential for use in future therapeutic strategies for MS, and researchers – including many funded by the National MS Society – are exploring these possibilities. Here are just a few examples of progress stemming from this exciting field.

Enhancing Myelin Repair

Growth factors originate from various sources within the body. Many are versatile, and can exert different effects on tissues and cells throughout the body, including the nervous system. The immune attack in MS targets the myelin sheath that insulates nerve fibers and nerve fibers themselves. Studies of brain tissue indicate that some repair of myelin does occur during the course of disease. Society grantee Steven W. Levison, PhD (Pennsylvania State University, Hershey) is investigating a possible role for ciliary neurotrophic factor (CNTF) in promoting this repair. Previously, Ralf Giess, MD and colleagues (University of Wurzburg, Germany) reported that CNTF is elevated in the spinal fluid of people with MS, and people who are genetically unable to make CNTF experience an earlier onset of disease and a more severe disease course (Archives of Neurology, March 2002).

Levison theorizes that CNTF appears as a consequence of damage in the brain and spinal cord and that it triggers the production of factors that could enhance the possibility of repair. Now, Levison is analyzing the course of myelin damage and repair in mice that are genetically engineered to produce an excess of CNTF. His team recently reported results in studies in mice recovering from virus-induced myelin damage (Neurobiology of Disease, July 2003). Levison found that astrocytes – cells that perform several support functions in the brain and spinal cord – produce CNTF during phases of myelin repair. This study may provide key information to developing strategies that promote myelin repair in MS.

In 1996, Society grantee Ben A. Barres, MD, PhD (Stanford University, CA) reported that CNTF accelerates the development of oligodendrocytes – the cells that make myelin – by enhancing the proliferation of immature oligodendrocytes (Molecular and Cellular Neurosciences, August 1996). Recently, Bruno Stankoff, MD, and colleagues (Hôpital de la Salpêtrière Paris) reported that CNTF increased myelin repair not by increasing the quantity of oligodendrocytes, but by enhancing the final maturation of these cells, and thus having a strong effect on the synthesis of myelin (The Journal of Neuroscience, November 2002). The authors note that these findings raise the possibility for developing myelin repair strategies in MS using CNTF.

Myelin-repair capabilities also are reported for glial growth factor 2 (GGF2). Barbara Canella, PhD, and colleagues (Albert Einstein College of Medicine, New York) found that mice treated with a manufactured form of this protein displayed more myelin repair than untreated controls, and experienced decreased disease severity and fewer relapses (Proceedings of the National Academy of Sciences, August 1998). Acorda Therapeutics, Inc. acquired the rights to this compound in 2002, and is moving forward with its preclinical development in preparation for clinical trials in MS.

A Role in Nerve Protection
and Repair?

The first growth factor known to be active in the brain tissue of people with MS was brain-derived neurotrophic factor (BDNF). Martin Kerschensteiner, MD (University of Zurich) and colleagues reported that this factor – which is known to help nerve cells survive during development and following injury – is produced by immune cells within MS lesions, and is increased when substances that trigger inflammation are increased (Journal of Experimental Medicine, March 1, 1999). BDNF was then able to rescue nerve cells from death! The team noted that “importing” BDNF into the brain and spinal cord using immune cells represents an attractive candidate for development as an MS treatment.

Society grantee Marie T. Filbin, PhD (Hunter College, New York) has found further evidence for the benefits of BDNF. Her team previously identified a molecule called myelin-associated glycoprotein (MAG) – a molecule within myelin – as an inhibitor of nerve regeneration. By giving BDNF to nerve cells before exposing them to MAG, this regeneration block was overcome. But if BDNF was given with MAG, there was no such effect, and repair remained inhibited (Neuron, January 1999). This finding is important for encouraging the regrowth of nerves, in animal models and eventually in humans with MS.

One treatment currently used for MS may actually take advantage of BDNF’s neuroprotective capabilities. Copaxone (glatiramer acetate) is a synthetic compound that simulates a protein in myelin. Suhayl Dhib-Jalbut, MD (Now at Robert Wood Johnson Medical School, New Brunswick, NJ) and colleagues studied the T cells of 12 people treated with Copaxone. They reported that levels of BDNF were higher in T cells reacting to Copaxone than those reacting to genuine myelin proteins (Journal of the Neurological Sciences, November 2003). Whether or not Copaxone in fact protects nerve fibers or enhances their repair remains to be determined.

Rescuing Myelin-Making Cells

Research shows that growth factors usually associated with organs other than the brain may also be active within the central nervous system. Society grantee Jeffrey L. Mason, PhD (now at Thomas Jefferson University, Philadelphia) and colleagues determined that insulin-like growth factor-1 (IGF-1, which primarily originates in the liver and mainly acts to battle inflammation and heal wounds throughout the body) is required for the survival of oligodendrocytes and is found within areas of myelin damage in mice. If IGF-1 is not present, immature oligodendrocytes are killed, possibly by toxic factors released by immune cells. They suggest that IGF-1 might be used to inhibit oligodendrocyte death in MS (The Journal of Neuroscience, August 2003).

Tevor J. Kilpatrick, MBBS, PhD, and colleagues (The Royal Melbourne Hospital, Parkville, Australia) reported that administering leukemia inhibitory factor (LIF, an immune messenger protein that can affect a wide range of cells) to two mouse models of MS-like disease prevents the death of oligodendrocytes (Nature Medicine, June 2002). The authors suggest that the results serve as the basis for developing an MS treatment strategy, and Kilpatrick is currently funded by the Society to explore this possibility further.

Promise for the Future

The study of growth factors and their potent capabilities within the central nervous system is a promising area of MS research, and already has yielded novel strategies that may lead to new treatments for people with multiple sclerosis.

Hope it's of use to someone! Take it easy!