Early in discussions with potential investors or corporate partners, we are frequently asked, “How do these formulations work, and how can you have so much to offer when you’re so young a company?”
Beech Tree Lab’s (BTL) product candidates originate from a long history of discovery, research, and early-stage development, a history that focuses on the inventions of John McMichael, PhD, founder and president of BTL, and his clinical and laboratory associates. For example, stemming from international recognition for a diagnostic test for multiple sclerosis (MS) developed by Dr. McMichael and his colleagues in the mid-1970s, he was asked by a physician in Mobile, Alabama to help devise a new therapeutic approach to MS. This was Dr. McMichael’s initiation to therapeutics. The physician was Joseph A. Miller, MD, a world-recognized allergist considered today the father of a unique form of allergy treatment called provocative neutralization.
It has been commonly accepted that by using low levels of the same insulting agent that causes an allergic reaction, one could turn off the aberrant immune response that resulted in symptoms of disease: a typical allergy approach. That is, if a person is allergic to ragweed, then a small amount of ragweed extract is introduced into the person in order to desensitize him so he doesn’t react to ragweed anymore. The unique aspects of Dr. Miller’s approach was that he used, as in this case, concentrations of ragweed extract that were much lower than those used for traditional desensitization. The significance of this difference is that the two concentrations—traditional for desensitization, much lower for neutralization—likely results in manipulation of different components of the immune response.
That is to say, with desensitization the antibodies against an insulting agent are tied up, so to speak, and so are not available to attack the antigen, whereas with neutralization antibodies are not formed in the first place. In both instances, the attempt made is to interfere with the process that evokes the symptoms of a disorder.
Upon meeting Dr. McMichael, Dr. Miller inquired as to whether his approach to treating allergies could be expanded to address disorders not of the classic allergic variety but diseases which had a recognized immune or autoimmune component. Dr. McMichael spent time with Dr. Miller while studying patients and various diseases. Upon reflection, Dr. McMichael noted two things that were characteristic of all of the MS patients. One was that they all had elevated levels of antibody to rubeola (measles) virus, which was consistent with reports in the literature. The other observation was that they all described being weather sensitive, as do people with joint disorders who can predict weather changes because their joints hurt. “If my left knee hurts, I know in 48 hours it’s going to rain,” that sort of statement.
Clinically, this type of statement may suggest histamine sensitivity. Histamine is a molecule in the body released under different kinds of stress, and the body’s reaction to histamine can result in the type of joint pain that arthritic patients experience. Consequently, Dr. McMichael wondered what would happen if the MS patients were desensitized, or more appropriately neutralized, to those two substances: histamine and rubeola virus.
Stemming from this initial investigation, Dr. McMichael soon teamed with Kenneth Unice, DO, a physician in private practice in western Pennsylvania. Dr. Unice found interest in Dr. McMichael’s work and together they studied the effects of this novel treatment on his MS patients under Dr. McMichael’s first investigative new drug (IND) application with the FDA. This collaboration was also the beginning of Dr. McMichael’s establishing an extensive professional network consisting of physicians, veterinarians, and medical scientists.
The result of this study with Dr. Unice was encouraging. Over 70 percent of 400 patients showed a positive response to this novel therapeutic response. This didn’t mean that they no longer had MS. It did indicate that they could tolerate their symptoms better or that their symptoms were lessened. MS is not considered an allergic disease. Nor do an unusual number of MS patients suffer from allergies. However, what this demonstrated to Drs. Unice and McMichael was that these two substances might provide a key to regulating not only the immune response but also the other two regulatory systems of the body, the endocrine (hormone) and the nervous. Recognizing that these three systems—immune, endocrine, and nervous—are intimately associated and that by manipulating one the others might also be affected, the groundwork was laid for investigating a new approach to treating a variety of disorders reflecting regulatory dysfunction.
It was by first studying allergies and allergy-associated techniques that Dr. McMichael and his team learned that the use of low doses of naturally-occurring molecules could induce a predictable spectrum of biological responses. Indeed, in what is rapidly leading to a novel platform for treating a variety of chronic disorders, by studying specific diseases ranging from MS to cancer to lupus and so forth, Dr. McMichael’s network found that by using low concentrations of agents specific to the disease in question they could manipulate the immune response, or one of the other regulatory systems, with a consequent relief of symptoms—the degree of which could result in control or reversal of disease.
Concurrent with these studies, Dr. McMichael patented the respective formulations. As a result of a growing patent portfolio and the on-going anecdotal successes of practitioners, in 1993 Dr. McMichael founded Milkhaus Laboratory, Inc. (MLI), in order to facilitate bringing these therapies to market.
Over the next ten years, MLI successfully conducted 13 FDA-authorized clinical trials centering on respiratory illness, prostate disorders, cancer, and chronic fatigue syndrome. During this time, John McMichael and MLI continued to expand their patent portfolio. Indeed, Dr. McMichael’s research led to promising early results in treating Alzheimer’s disease using beta-Amyloid protein as the therapeutic agent. Resulting from this investigation, he was awarded more than 30 patents that were then licensed by MLI to Elan Corp, plc, to afford that company protection in its own efforts to combat Alzheimer’s using a similar approach. Elan’s product candidate is now in FDA-authorized clinical trials, their technology stemming in part from Dr. McMichael’s initial work
Following a failed treasury-depleting major FDA-authorized trial in 2004, the MLI Board of Directors decided to shift the company’s focus from pharmaceuticals to nutraceuticals of botanical origin. Dr. McMichael, in turn, remained committed to the more rigorous development of pharmaceutical products while recognizing that several product candidates were better suited for the nutraceutical market. As pre-clinical successes unabatedly continued, Dr. McMichael renewed his vision of delivering safe and efficacious products and founded BTL in 2005. In anticipation of a potential stream of income from royalties, MLI then licensed their technologies to BTL. Core MLI personnel, including senior research scientist Stephen Mamber, PhD, followed with a lateral move to BTL.
Based on this proven model of discovery and development, BTL continues to expand its patent portfolio as more is learned about diseases and more is learned about new molecules that can be used. Moreover, as long as a disease contains a component relating to regulatory dysfunction, BTL investigators are continuing to find new ways to control or reverse disorders and simply allow the body to carry out its normal processes and restore health.
Currently, BTL is in the process of filing two IND applications as a prelude to formal FDA-authorized clinical trials. BTL researchers at its Providence, Rhode Island, laboratory and collaborating investigators at several universities are conducting basic science studies in order to move other product candidates further along a robust pipeline. Supporting the idea that this research is forming a new platform for treating a range of chronic disorders, additional patent applications are also being prepared and filed.