MEDICINE / HEAD INJURIES : New Drug May Help Lessen Effects of Severe Trauma
A new genetically engineered drug could increase the likelihood of surviving severe head injury by as much as 20%, researchers said this week.
The new treatment could spell the difference between a job and independent living and life in a coma, or even death, for as many as 50,000 Americans each year, Dr. J. Paul Muizelaar of Wayne State University in Detroit told the Congress of Neurological Surgeons in Chicago on Monday.
Muizelaar and his colleagues at 28 other hospitals around the country administered either the drug, called PEG-SOD, or a placebo to 463 patients who suffered severe head injuries, most of them in automobile accidents.
Among those given the sham treatment, 46% were able to return to work or live independently. Among those receiving the optimum dose of the drug, however, 55% were able to do so.
Because more than 500,000 Americans are hospitalized with head injuries each year, neurologists “have said that even an improvement of a few percentage points (in survival) would be clinically important,” Muizelaar said. “This is even better than that.”
“We feel the results are very significant,” said Dr. Kenneth S. Waxman, a neurosurgeon at UC Irvine. “PEG-SOD is . . . the first (such medication) shown to actually work in a controlled trial.”
Head injury is the leading cause of death and disability in children and young adults in the United States, accounting for 13% of all injuries, according to the National Institute of Neurological Disorders and Stroke. Conservative estimates suggest that 2 million people suffer a traumatic brain injury each year, with 500,000 requiring hospitalization and 75,000 to 100,000 resulting in death. More than half of those injuries arise from motor vehicle accidents.
Males are twice as likely as females to suffer head injuries, and most survivors are between the ages of 15 and 24. Nationwide, the economic costs of head injuries total more than $25 billion per year, according to the stroke institute, with the lifetime cost for a single survivor reaching as much as $9 million.
A substantial fraction of the deaths and damage arises from so-called secondary brain damage, the swelling and pressure that develop in the days after the accident. When the flow of oxygen and sugar to the brain is impaired by trauma, toxic chemicals called oxygen free radicals are created. The free radicals damage tissues directly and also produce swelling that can be extremely damaging or fatal.
The body has a naturally occurring enzyme called superoxide dismutase (SOD) that destroys free radicals, but this system is overwhelmed by the trauma. A long series of animal experiments by Muizelaar and other researchers has shown that SOD produced by genetic engineering techniques can supplement the natural SOD activity and minimize damage. Scientists attached the SOD to a polymer called polyethylene glycol (PEG) so that it remains in the blood longer, thereby extending its therapeutic benefit.
Muizelaar said that the drug’s manufacturer, Sterling-Winthrop Inc., will probably apply to the Food and Drug Administration for marketing approval upon the completion of a second and larger clinical trial that is expected to be completed within a year.
The FDA has already placed the drug on the so-called fast track toward approval because it is used for a life-threatening disorder for which no treatment is currently available. Such approval is likely, Muizelaar speculated, because “it appears to me that it works and that it is also very safe.”
The results in the new study are similar to those obtained in a previous study on 104 patients used to determine the best dosage levels. Muizelaar said as many as 900 more patients are enrolled in the other ongoing study of the drug.
The failure of the drug in those patients who did not respond may have been due to the severity of the damage caused by the trauma, Muizelaar said. He also speculated that the response would be better if the drug were given immediately after the injury. On average, the drug was administered to patients in the study about six hours after their accidents.
“This is a sentinel finding . . . because it shows we’re on the right track,” added Dr. Steven L. Giannotta of USC. “Over the last 10 years there have been no major accomplishments that have altered the way we care for head injuries. This gives impetus to the search for medications that can have even greater impact.”
