New non-hormonal contraceptive (in the works)

New non-hormonal contraceptive

avoids side effects of the Pill

By Jeremy Laurance, Health Editor

Published: 17 October 2007

Almost 60 years after the development of the Pill, scientists have announced they are working on the first alternative oral contraceptive, and they hope it will be free of side-effects.

Instead of controlling the woman's monthly cycle, the new drug would work in an entirely different way by targeting a gene that controls female fertility and it would be completely reversible.

Unlike the existing Pill, it would not contain hormones and scientists hope it would have far fewer adverse effects. It could be delivered through a patch on the skin which would need to be worn for only a few days each month, when the woman was ovulating. Women who take the Pill complain of mood swings and nausea and are at higher risk of blood clots and high blood pressure. The Pill contains small doses of the hormones oestrogen and progestogen which block ovulation but cause side-effects.

The new contraceptive, which is in the early stages of development, would avoid these side-effects because it does not depend on manipulating hormones.

Instead it would allow ovulation to occur as normal but would prevent the sperm penetrating the egg by targeting a gene called ZP3. Blocking the gene prevents production of a protein that forms part of the coating of the egg which enables sperm to bind to the outer layer. The technique is based on RNA interference, which targets specific genes.

Dr Zev Williams, of Brigham and Women's Hospital in Boston, presented the findings at the American Society for Reproductive Medicine conference in Washington. He said trials on humans were a decade away and the drug had only been tested in mouse and human kidney cells. But the results had demonstrated "proof of principle" showing that it worked. "Mice that have ZP3 knocked out are infertile. They just don't get pregnant. If you could block this in women, you could prevent pregnancy from occurring. Our work is a proof of concept, in cell culture."

Dr Williams said there were only three kinds of contraceptive – hormones, IUDs and barriers – and there was an obvious need for a wider choice. "Since the 1950s we have had the entire biomolecular revolution in medicine, and yet these three options are still all there is. We simply don't have a contraceptive drug that is non-hormonal and reversible. What we are trying to do is to think about contraception in a new way. Obviously there are going to be big hurdles and it is going to take a lot of time, but the need is there and we think it can be achieved."

Some women derive benefit from the hormonal effects of the Pill because it regulates their monthly cycle or reduces menstrual pain. "But for women who use the Pill just as a contraceptive, a non-hormonal approach would be wonderful," Dr Williams said. "You could get all the benefits without the nausea, the headaches, the mood alterations, and the raised risk of thrombosis, stroke and heart attacks."

Andrew Sharkey, senior research associate in the Department of Pathology at Cambridge University, said: "The advantage of ZP3 is that it doesn't occur anywhere else in the body, so the effect is highly targeted. You can get weight gain with oestrogen and some pills have an effect on libido and mood and every woman has a different response. The oral Pill is nearly 60 years old and there has been no real advance since then."

How the process was discovered

RNA interference – which means, in scientific terms, silencing, or quelling – came about originally through experimentation among plant researchers during the 1990s. Although the aim was to produce darker flowers, what emerged were almost entirely white flowers, less pigmented and – crucially – indicating that 'chalone synthase' had been significantly decreased. It was used on other organisms such as worms and fruit flies, and in 1998 a paper in the journal Nature by the scientists Craig C Mello and Andrew Fire, introduced the concept of gene silencing and they won the Nobel Prize in

Pete Sampras & Thalassemia Minor

Sampras Suffers from Thalassemia
By Tom Tebbutt, The Globe and Mail

September 23, 1996

For the supremely talented Pete Sampras, it is unlikely that any opponent will prove as much of a challenge as thalassemia.

A September 10 story in The Globe and Mail speculated that the world No.1 suffered from some form of anemia, and it has been learned that Sampras has an inherited condition that is almost certainly thalassemia minor, a congenital form of anemia common among people in the Meditteranean.

Sampras's mother, Georgia, was born in Greece, and his father, Sam, is of Greek ancestry.

Having that thalassemia minor means the 25-year old Sampras has a low count of hemoglobin, which carries oxygen in red blood cells. "It's a mild to moderate anemia and you lead a normal life with no reduction in life expectancy," Toronto hematologist Dr. George Kutas explained. "A weekend hacker probably wouldn't even notice it."

Thalassemia minor is inherited from one parent. The much more serious thalassemia minor results if both parents pass on the defective gene. "Sampras would be very sick and not playing tennis if he had " thalassemia major," Kutas said emphatically.

The more serious form is characterized by the need for continuing blood transfusions, stunted growth and the many possible complications arising from multiple transfusions.

"Thalassemia minor is a lifelong thing that people adjust to," Kutas said. "The prognosis for Sampras over the next few years is not much different than it has been, because thalassemia is set at birth and it doesn't get worse or better.

"There haven't been many world-class athletes with thalassemia, so there's no literature available on the subject. We don't have studies to prove it, but due to the limited oxygen- carrying capacity, an athlete might get to the point where he could no longer increase his cardiovascular output because of a limited number of red blood cells. That would impair the extra effort required at that top level of sport."

Inhaling oxygen, as is done in some sports, notably football, would not be a solution for Sampras. "That probably wouldn't help," Kutas said, "because there's nothing wrong with the red blood cells carrying the oxygen, it's just that he's not making enough hemoglobin."

What could Sampras do during a match? Other than getting a transfusion " before the tournament, there's not much you can do," Kutas said. The effects of a transfusion (but not his own blood, because it's already low in hemoglobin) would easily last two week of a tournament like the U.S. Open (which Sampras won two weeks ago). But it's unlikely he would have one because of all the possible negative side effects.

A blood transfusion would not be considered to be blood doping, a dangerous practice used by some world-class athletes. "Blood doping is when you have normal hemoglobin levels and you want exceptional hemoglobin levels," Kutas explained. "In Sampras's case, if he did it, it would be to get his hemoglobin to normal levels."

What advice would Kutas have for Sampras? "It's obvious that in a long "match he gets into more trouble," he said. "One minute he's hunched over "leaning on his racquet [as against Alex Corretja in a memorable match at the U.S. Open] and then the next he's serving an ace at 110 miles an hour. I'd basically tell him only to push himself to a certain point."

Should Sampras be watching what he eats? "There's nothing he can really do in terms of diet," Kutas said, "because it's a condition you have from birth-actually it's often misdiagnosed as a lack of iron."

In Sampras's case, if his mother had the gene, she would likely have learned of her condition during tests when she was pregnant with one of her three children. "A doctor doing blood tests can pick it up easily," Kutas said. "If hemoglobin levels are lower than normal, they'd just follow up with a simple test to prove it."

Sampras would have a 50-per-cent chance of passing on the condition if he had children. However, if the child's mother also carried the gene, " there's a 25-per-cent chance that their offspring would have thalassemia major.

As for the effects on Sampras's career, it's clear that he will continue to have problems when he gets involved in long, exhausting matches. But especially at tournaments such as Wimbledon where the points are over quickly, he should be able to perform well and possibly add to his impressive total of eight Grand Slam wins.

If Sampras admits to having thalassemia minor, it would help silence critics who have interpreted his frequent physical breakdowns as being " the result of poor preparation and conditioning.

Beta-Thalassemia & Epo

from the Journal of Athletic Training
Volume 37 • Number 2 (Supplement) • June 2002

A 22-Year Old Division I Male Football
Player Diagnosed With Beta-Thalassemia
Minor Blood Disorder: A Case Study
O’Brien MS, Ransone JW, Smith KB:
College of Education, Oklahoma State
University, Stillwater, OK
Personal data
A 22-year-old division one collegiate football
player with no remarkable medical history complains
of fatigue and inability to recover from bouts
of exercise.
Physical signs and symptoms
The athlete presented symptoms of cardiovascular
(CV) deficiency (shortness of breath, irregular
CV endurance) for which, the team physician ordered
a blood work up including baseline levels of
comprehensive metabolic profile (CMP) and complete
blood count (CBC).
Differential diagnosis
Differential diagnosis of signs and symptoms include
iron deficiency anemia, sickle cell anemia,
beta thalassemia minor, hereditary leptocytosis,
minor heterozygous beta thalassemia intermedius
Results of diagnostic imaging/laboratory tests
After a baseline CMP and CBC were completed
revealing depressed levels of hemoglobin, further
tests were ordered by the team physician. Results
of these tests coincided with hypochromic
microcytic anemia. A sickle-dex was conducted
and was found to be positive. Results of the
hemoglobin electrophoresis conducted thereafter
indicated a depressed amount of hemoglobin A
(90%, reference 93.5%- 98.3%) revealing the betathalassemia
minor disorder. Additionally, initial
blood work presented low levels of blood erythropoietin
levels (4.7 mu/mL, reference 7.3- 27.7),
hemoglobin (11.8 g/dL, reference 14.0-18.0 g/dL),
and hematocrit (37.4%, reference 42.0- 52.0%).
Blood work conducted one week post Procrit®
injections exhibited elevated hemoglobin (16.1 g/
dL) and hematocrit (48.7%). Follow up measures
obtained one month post injections revealed
a marked decrease in blood erythropoietin levels
(3.8 mu/mL) and normal levels of hemoglobin
(14.9 g/dL), and hematocrit (45.6%)
Clinical course
To treat the beta thalassemia minor anemia, the
team physician prescribed the administration of
10,000 units of Procrit® (erythropoietin supplement)
according to the athletes body weight, three
times per week for one month to restore normal
levels of hemoglobin production, 325 mg of
Ferosul® (ferrous sulfate) and 500 mg of ascorbic
acid daily.
Deviation from expected
Thalassemia minor is a blood anemia characterized
by a genetic anomaly that affects the number of
hemoglobin proteins of a single red blood cell and
their ability to carry oxygen. Thalassemia minor
is not typically seen in the athletic population
and treatment for the disorder has not been
thoroughly addressed. In this particular case, the
prescription of Procrit erythropoietin was decided
upon to elevate hemoglobin levels and re- establish
the athlete’s oxygen carrying capacity to that of
normal levels required for athletic competition.
The athlete responded well to this treatment and
continued full participation in football activity.