The movie 'Limitless' features the character Eddie Morra (played by Bradley Cooper) as an average author who gains genius intelligence after taking a pill. He swiftly becomes fabulously wealthy, leveraging his superhuman mental faculties to write a bestseller, perfectly navigate the stock market, and rise to political power. He soon finds out, however, that there are dangerous long-term sideeffects to the drug. While the concept of 'Limitless' was pure science-fiction, many moviegoers began to wonder if our modern science could one day invent such a drug. Given advances in neurogenesis and a recent patent granted to the company Neuralstem, there is hope that the intellectual abilitles portrayed in the movie 'Limitless' may someday become reality.

It is a commonly held belief that adult humans do not regenerate brain cells — that once they’re gone, they’re gone. Recent studies suggest, however, a strong likelihood that a cellular mechanism for neurogenesis (new brain cell production) within adult human brains does exist as both a normal physiological process and a self-repairing pathway. This production of new brain cells is believed to occur primarily within the hippocampus, an area of the brain that affects short-term and long-term memory. The studies further suggest that such adult-generated neurons contribute to brain physiology with respect to learning and memory functions. Studies in healthy young rodents estimate that approximately 3,000 to 15,000 new cells are born in the hippocampus each day, about 60 percent of which express early neuron-specific proteins.

This trend is likewise observed among primates and human patients. Such significant quantities of new neurons suggest that neurogenesis significantly contributes to normal hippocampal physiology. One study reported that inhibition of neurogenesis in adult rat hippocampus, in the absence of the destruction of existing neurons, caused impaired memory function.

The ability to target and increase hippocampal neurogenesis may therefore have significant implications for diseases presenting cognitive deficits. A neurogenic drug or agent that enhances the process of generating new neurons would be beneficial in countering and treating neurological diseases, including Alzheimer’s, mild cognitive impairment, dementia, age-related cognitive decline, stroke, traumatic brain injury and spinal cord injury, as well as neuropsychiatric diseases, such as depression, anxiety and schizophrenia.

Neuralstem, Inc., a company devoted to the development of neural stem cell technology, received a patent for just such a neurogenic drug on October 4, 2011, entitled “Compositions to Effect Neuronal Growth.” The patent is directed to both composition and method claims, specifying a “method for inhibiting neuronal death or for inducing proliferation and differentiation of a neuronal progenitor cell into a neuron” by contacting the neuron or cell with an effective amount of the composition claimed. The patent summary discloses that:

The compounds of the present invention are shown to stimulate endogenous neural stem cells capable of differentiating into neurons in adult human brains to proliferate and to differentiate into functional neurons in vivo. The additional neurons may enhance the cognitive ability of the subject and significantly extend the ability to perform cognitive tasks . . .

In short, the invention is directed to a chemical compound that can cross the blood-brain barrier to stimulate the development of preexisting stem cells into new neurons in adult human brains and may be effective either in a disease state or in a healthy state. The compound may also inhibit the brain cell destruction (apoptosis) that occurs both as a natural part of age-related cognitive decline and in conjunction with neurodegenerative diseases.

The enhanced production (neurogenesis) and inhibited destruction (neuroprotection) of these brain cells may then contribute to improved mental activity in the subject. In addition to the compound’s ability to ameliorate cognitive function in adults, the patent further envisions the possibility of delivering the compound in utero or early postnatally to improve brain or spinal nerve development in fetuses and infants.

The implications of this invention are obvious; the prospect of a drug that can both stimulate neurogenesis and prevent neuron apoptosis is novel and exciting. This compound not only is theoretically useful in preventing further brain cell loss but can reverse degeneration by promoting neurogenesis. In theory, this drug could replace all damaged neurons in the recipient. Additionally, this compound functions by a completely different mechanism than those currently utilized by drugs intended to treat depression, schizophrenia and other cognitive diseases.

Many of these currently administered treatments are not physically tolerable by patients using them and are quickly abandoned. Furthermore, many neurodegenerative diseases, such as Parkinson’s disease, do not currently have any acceptable treatment. The compound disclosed in this patent may provide a tolerable alternative treatment for those who have run out of viable options, and may be a lifeline for those for whom treatment has not previously been an option.

Yet this compound presents very real concerns as well. Promoting neurogenesis does not address the root cause of the disease promoting neurodegeneration in the first place. The plaques, neurofibrillary tangles, and mis-formed proteins associated with the cognitive diseases that are slowing or stopping neurogenesis, or stimulating neuron apoptosis, are not being affected by this treatment. Promoting brain cell growth does not cure the disease process at the higher level. As a result, this treatment may require continuous administration to maintain some level of efficacy: the patient will need constant jumpstarts on his neurogenesis to keep up with the brain cell loss caused by his underlying disease.

For older patients hoping to retain some cognitive ability in their final years, the need for regular treatment may not be an issue. Treatment of neurodegenerative diseases in younger patients may present more of a problem. Additionally, little is known about the long-term effects of treating these cognitive diseases by promoting neuron growth. Could the disease become more aggressive to the degree that this neuron-replacing treatment could not keep up? And what happens to the diseased neurons? Despite increased healthy neuron production, the mis-formed neurons are still present and part of the patient’s nervous system circuitry. How will the healthy and diseased cells compete?

Patent approval is only the first step in a long and arduous process towards gaining FDA approval. Neuralstem is currently in the midst of Phase I clinical safety trials for another neural stem cell-based compound directed at preventing and treating Lou Gehrig’s disease, as well as one for chronic spinal chord injury. To be sure, these innovations present exciting new possibilities in the effort towards understanding, treating and preventing cognitive diseases. While the pharmaceutical wizardry of the genius pill shown in 'Limitless' has not yet been achieved, the echoes of its future steps can already be heard.

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