New Variations On Old Drugs Promote Nerve Regeneration

April 02, 1997

Researchers at Johns Hopkins and Guilford Pharmaceuticals Inc., have successfully modified a group of established drugs to stimulate nerve growth without suppressing the immune system.

The researchers say the development is a critical step toward using the new compounds as treatments for a wide range of neurodegenerative diseases like Parkinson's disease or multiple sclerosis, or brain injuries from stroke or head trauma.

"We showed that these compounds can cause recovery of functions and behaviors previously lost to nerve damage in lab animals," says Solomon Snyder, M.D., Hopkins director of neuroscience and principal author on the paper, which appears in this month's Nature Medicine.

"We believe this is the first demonstration through an orally administered treatment of a significant regenerative effect on nerve cells without suppression of the immune system." Immunosuppressive drugs like cyclosporin A and rapamycin were originally developed to prevent a patient's immune system from rejecting an organ transplant. When researchers looked for the compounds immunosuppressive drugs bind to in the body, they found a group of proteins called immunophilins.

"These are proteins frequently used by the cell for what we call signal transduction," explains Snyder. "They bind to something outside the cell, and as a result of that binding cause changes inside the cell--make it less likely that an immune cell will proliferate, for example."

Hopkins scientists discovered that brain cells have 10 to 50 times more immunophilins than immune cells and that immunophilins in the brain are linked to a variety of important nerve cell functions, including the ability to regenerate lost branches of the cell and generate new branches.

Immunosuppressive drugs bind to immunophilins; together, the two interact with a protein called calcineurin to suppress the immune system. Researchers at Hopkins and Guilford, using new techniques from molecular biology and a field called combinatorial chemistry, attached chemical structures to the drugs that prevented them from binding to calcineurin but did not affect their ability to attach to immunophilins.

Scientists at Hopkins and Guilford put the new drugs to the test alongside the original immunosuppressive drugs, first in studies of chicken nerve cells in the lab, and later in rats whose sciatic nerve had been crushed. There was no significant difference in the new drugs' ability to stimulate growth of new nerve cell branches and cause regeneration of lost branches.

"The new drugs were even able to regenerate the protective myelin sheath surrounding the branch, which is critical to recovery of function," says Snyder.

Representatives from Guilford hope to begin clinical trials of some of the new drugs in a year or more. Guilford is a private biopharmaceutical company based in Baltimore.

Under an agreement between Johns Hopkins University and Guilford, Snyder and Ted Dawson, M.D., Ph.D., another Hopkins author on the Nature Medicine paper, are entitled to a share of royalties received by the University from Guilford. The University owns stock in Guilford, with Snyder and Dawson having an interest in the University share under University policy. Snyder serves on the Board of Directors and the Scientific Advisory Board of Guilford, is a consultant to the company, and owns additional equity in Guilford. This arrangement is being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

Other authors on the Nature Medicine paper were Joseph Steiner, Maureen Connolly, Greg Hamilton and Heather Valentine, of Guilford; and, Ted Dawson, and Lynda Hester of Hopkins. The studies were funded by Guilford and the National Institutes of Health.


Media Contact: Michael Purdy (410)955-8725


Johns Hopkins Medical Institutions' news releases are available on a PRE-EMBARGOED basis on EurekAlert at and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to or

On a POST-EMBARGOED basis find them at,, Newswise at or on CompuServe in the SciNews-MedNews library of the Journalism Forum under file extension ".JHM", Quadnet at or ScienceDaily at

Johns Hopkins Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to