For decades it didn’t look like clioquinol was going to qualify for the Pharmaceuticals Hall of Fame.

The hydroxyquinoline antibiotic had been used since World War II to treat amoebic infections and shigella gastroenteritis until being blamed for an enormous outbreak of subacute myelo-optic neuropathy in Japan in the 1960s.

There was little scientific reasoning behind the presumed association, and the drug had been used safely by millions before the epidemic but hey, other antibiotics were available to treat the conditions in question so why take a chance?

So the drug passed quietly into retirement, presumably never to be heard from again.

But then out of nowhere, recent animal studies have surfaced purporting to show that clioquinol reverses progression of not one but 3 seemingly unrelated neurodegenerative conditions–Alzheimer’s, Huntington’s and Parkinson’s disease, respectively.

That’s got to be the greatest comeback since Cream rocked Madison Square Garden in 2005.

“The drug affects a gene which when inhibited can slow down aging,” Siegfried Hekimi told the Journal of Life Sciences. “The implication is that we can change the rate of aging. This might be why clioquinol is able to work on this diversity of diseases that are all age-dependent.”

Hekimi and colleagues at McGill University recently reported in the Journal of Biological Chemistry that clioquinol inhibits a mitochondrial enzyme known as CLK-1, or simply “clock-1.” 
 
The mechanism by which clioquinol inhibits CLK-1 remains unclear. “One possibility is that metals are involved as clioquinol is a metal chelator,” Hekimi explained.

Is Oprah’s weight up or down this month and really, is it possible to lose a lot of weight and keep it off for years without bariatric surgery?

It’s up—much to the dismay of the army she retains to keep it down—but maybe she needs guru replacement surgery because the results of a study in the International Journal of Obesity suggest that behavioral modifications involving diet and exercise can indeed cause sustained weight loss.

“Our findings suggest that it’s possible to maintain large weight losses through intensive behavioral efforts…regardless of whether you lost weight with bariatric surgery or through non-surgical methods,” concluded Dale Bond, the study’s lead author.
 
Bond is director of the Center for Behavioral and Preventive Medicine at Miriam Hospital.
 
Bond’s study matched bariatric surgical patients with those who went the behavior mod route. The 315 participants had lost 124 pounds on average and had maintained the lower weight for 5.5 years before the study began.

During the 2-year follow-up, the scientists found no difference between the groups in caloric intake or the amount of weight regained, which was about 4 pounds per year.
 
However bariatric patients consumed more fat and fast food and reported less conscious control over food intake. They also had an increased risk of depression and reported higher stress than the behavioral group.

Only a third of the bariatric patients engaged in physical activity whereas 60% of those in the non-surgical group did.
 
 “These findings underscore the need for eating and activity interventions focused on bariatric surgery patients,” Bond, told TJOLS. “Future research should focus on ways to increase and maintain physical activity and better monitor psychological parameters in bariatric surgery patients.”

The FDA approved ImClone’s Erbitux and Amgen’s Vectibix in 2004 and 2006 respectively for the treatment of colorectal cancer.

Then, research findings published last year revealed the 2 monoclonal antibodies only work in 60% of the population whose tumors do not have a mutation in the so-called K-RAS gene.

So in a meeting last month with the FDA’s Oncology Drugs Advisory Committee, the drug companies pressed the agency to alter their drugs’ labels so as to warn physicians not to treat patients with the mutant K-RAS gene.

The research prompting the request was a large, multinational trial presented at the American Society of Clinical Oncology meetings by Eric Van Cutsem of University Hosptial, Leuven, Belgium.

At the meeting, ImClone’s Sr. VP Hagop Youssoufian described the findings as “nothing less than transformational.”

In fact, the trial results compelled the European Medicines Agency to recommend that physicians establish patients’ K-RAS status before prescribing the drugs, and just yesterday the American Society of Clinical Oncologists made a similar recommendation.

Meanwhile, Amgen had cut a deal with UK-based DxS to provide its K-RAS mutation screening kit in conjunction with Vectibix in the US. The deal could translate to more revenue for Amgen if the FDA changes the drug label.

More than $600 million dollars per year in completely worthless treatments, if the above study is right, would be saved if the drugs were not given to patients having the mutation.
 
The Advisory Committee’s response was the scientific version of “whoa Nelly!”

It wants more data before it recommends companion diagnostics for targeted cancer drugs in general, and claims to have issues with retrospectively identified biomarkers.
 
Such studies can introduce bias, the Committee asserted.

A recent study from McMaster University revealed that medicalized terms carry a weightier, more serious connotation than corresponding lay terms for the same condition, but only if they had recently entered the lexicon.

How good are you at deciphering ridiculous medical jargon? Let’s find out!

Match the normal words on the left with the fancy ones on the right. Note that the medical terms corresponding to the normal words 1 to 8 had, according to the McMaster scientists, entered the lexicon years hence, so they don’t carry a more ominous connotation.

It’s the medicalized terms for 9-16 that are the troublemakers.

Normal words                          Medicalized terms
1. High blood pressure                a. Hypercortisolism
2. Lou Gehrig’s disease               b. Hypertrichosis
3. Stroke                                           c. Erectile dysfunction disorder
4. Gall bladder disease                d. Seborrheic dermatitis
5. Sore throat                                 e. Amyotrophic lateral sclerosis
6. Cushing’s disease                      f. Myocardial infarction
7. Celiac disease                            g. Hypertension
8. Heart attack                               h. Pharyngitis
9. Impotence                                  i. Gluten enteropathy
10. Male pattern baldness           j. Androgenic alopecia
11. Chronic fatigue syndrome  k. Myalgic encephalomyelitis
12. Skin tags                                    l. Cerebrovascular accident
13. Excessive sweating              m. Gastroesophageal reflux
14. Dandruff                                   n. Cholecystitis
15. Impotence                              o. Hyperhydrosis
16. Excessive hairiness             p. Acrochordon

Answers: 1-g, 2-e, 3-l, 4-n, 5-h, 6-a, 7-I, 8-f, 9-c, 10-j, 11-k, 12-p, 13-0, 14-d, 15-c, 16-b

Where do you fit?

Number Correct   Your Title
16                                   Einstein
14-15                             Ivy League
12-13                             Specialist
10-11                             Med Student
8-9                                 Politician
<8                                  Wall Street

How would you feel if your physician said you have heartburn, male pattern baldness or excessive sweating?

Now, how would you feel if she said you have gastroesophageal reflux disease, androgenic alopecia or hyperhydrosis?

The terms are synonymous but the medicalized ones carry different connotations, according to scientists at McMaster University.
 
To investigate the impact of medical terminology on perceptions of disease, Meredith Young and colleagues asked college students to rate medical and lay terms for several medical conditions.

When a condition was given a fancy medical label, students perceived it to be more serious, more legitimate as a disease, and less prevalent than when labeled using a lay term. The perceptions were not impacted by severity of the condition.

Thus a patient told she has gastroesophageal reflux disease is likely to think she is sicker than had she been told she has heartburn.  The authors speculate the difference can impact a patient’s sense of well-being and willingness to comply with care plans among other things.

The differences were observed only in conditions that had been recently medicalized (see post later today on this matter).

“A simple switch in terminology can result in a real bias in perception,” Young told the Journal of Life Sciences. The study co-author added, “These findings have implications for many areas, including medical communication with the public, corporate advertising and public policy.”

Karin Humphres, another co-author said “This is particularly important when you have…conditions that have become medicalized… through the influence of pharmaceutical companies, who want to make you think that you have a disease that will need to be treated with a drug.”

With cash burning holes in their pockets, withering prospects in their pipelines and Merck and Bristol Meyers Squibb recently having dipped into the BioTech trough, people expected more pharmaceutical companies to make moves in this space before long.

Sure enough, GlaxoSmithKline and Pfizer got BioTech deals done before the close of Q4.

GSK struck first, inking a global alliance with Dynavax to develop and commercialize toll-like receptor inhibitors for the treatment of autoimmune and inflammatory diseases.

TLRs are immune system receptors that activate inflammatory processes.

Terms of the deal call for GSK to give Dynavax $10 million up front in return for rights of first refusal on programs focusing on rheumatoid arthritis, psoriasis and lupus.

Dynavax carries out early R & D for these programs and can receive up to $200 million per program by hitting development milestones.

If GSK exercises its RFR to license the outputs of each program, it then assumes responsibility for ongoing development and commercialization. Dynavax would receive royalties on sales.

Pfizer bellied up to the bar too, signing a European marketing deal with Auxilium Pharmaceuticals for XIAFLEX , a first-of-its-kind, late-stage biologic used to treat Dupuytren’s contractures and Peyronie’s disease.

Auxillium gets $75 million upfront and can achieve $410 million more by hitting milestones, the first third of which are regulatory in nature, while the remaining are tied to sales.

The arms-length relationship in both cases is similar to the deal BMS cut with Exelixis a few weeks ago. More deals structured like them are sure to follow, as Big Pharma seeks arrangements that mitigate risk during the economic crisis.