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|Includes: CytRx Corporation (CYTR)

 Nerve regeneration after a stroke was a wishful thinking by sufferers from stroke-induced paralysis.  The location of nerve damage depends on the site of the brain area where a clot occurs. The paralysis could be a paraplegia or a quadriplegia or local, but still detrimental such as the nerve damage that affects eye sight, speech and swallowing, which causes the victims to choke when drinking liquids, or solid food that could result in aspiration pneumonia or suffocation.  

     When tissue plasminogen activator (t-PA) was introduced by Genentech, emergency physi-cians and paramedics succeeded, for the first time, in aborting stroke and heart attack before they cause damage to the central nervous system and heart muscle consecutively. The success of t-PA, though, depends on administering it in within the first three hours following the stroke. Many stroke victims, however, still develop early or late nerve damages with debilitating results. That’s why re-enervation, or nerve regeneration remains a big dream and any news of any pro-gress in this respect is appreciated and considered a victory. 

     Today, we have news that promises improvement in protecting and regenerating neurons fol-lowing stroke. Results of a study conducted with Cytrx’ drug arimoclomol under the direction of world-renowned stroke expert Dr. Michael Chopp of the Department of Neurology in the Henry Ford Health System, and other institutions demonstrated that the drug exhibited statistically sig-nificant neuroprotective and neuroregenerative effects in brain cells of animals induced with stroke. Arimoclomol was effective when administered ten hours or more after the onset of stroke.    

     Stroke-induced rats received an oral dose of arimoclomol or a control substance daily for 28 days with the initial dose administered either 6, 10, 24 or 48 hours after stroke. Sections of brain tissue were then evaluated for each of the following: 1) chaperone protein HSP70; 2) the num-ber of cells with the characteristic DNA cleavage caused by apoptosis; 3) the microglial cell marker IB4-receptor; or 4) a marker for newly developing brain cells called double-cortin. 

     Detailed cellular analysis these rats brains showed a significant increase in HSP70 - molecu-lar chaperone expression. It showed a decrease in apoptosis and of microglial cells that cause inflammation. Most importantly, the drug resulted in an increase in the number of developing neurons sprouting new projections, called neurites, which are indicative of neuroregenera-tion. 

HSP70 and doublecortin were detected with specific antibodies to the respective proteins, DNA cleavage was detected by a standard assay called TUNEL, and IB4-receptor was measured by binding to IB4-ligand.

     Despite the fact that Cytrx expected arimoclomol to increase HSP70 expression and therefore might prevent cells from undergoing apoptosis, it still was thrilled to discover that the drug has controlled the proliferation of inflammatory microglial cells and stimulated neuroregenera-tion as well. These latter effects may explain arimoclomol’s ability to restore brain function even when administered well after the stroke event, because the negative effects of inflammatory cells and the positive effects of neuroregeneration occur much later than the initial damage. 

    CytRx is expert in molecular chaperone regulation technology. The firm has two orally administered, clini-cal-stage drug candidates and has recently discovered a series of additional compounds that may provide additional drug candidates. Cytrx’ drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of "molecular chaperones." Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.

CytRx expects the new drug results and the information generated about its action to attract po-tential pharmaceutical or biotechnology partners for further development of arimoclomol. Attrac-tive also to wealthy firm might be the fact that arimoclomol’s clinical testing for stroke recovery could be relatively inexpensive, as more patients could be treated at fewer sites due to the ex-panded therapeutic window. 

The CytRx pipeline comprise cancer programs, including tamibarotene in a registration study for acute promyelocytic leukemia (NYSE:APL) and two other drug candidates based on its industry-leading molecular chaperone technology, which aims at repairing or degrading misfolded proteins associ-ated with disease. 

CytRx maintains a 39% equity interest in publicly traded RXi Pharmaceuticals(NASDAQ:RXII). 

Disclosure: No Positions