Thursday, April 03, 2008

Another Disorder That Increases With the Age of the Father Polycystic Kidney Disease


© Newswise.All Rights Reserved.
Source: American Society of Nephrology (ASN)

Released: Tue 01-Apr-2008, 11:30 ET Embargo expired: Wed 02-Apr-2008, 12:00 ET
Printer-friendly Version
Experiments Point to New Treatments for PKD

Contact InformationAvailable for logged-in reporters only
DescriptionA family of small molecules called CFTR inhibitors show promising effects in slowing the progression of polycystic kidney disease (PKD), the most common genetic disease of the kidneys, according to preliminary research reported in the July 2008 issue of the Journal of the American Society Nephrology.
Newswise — A family of small molecules called CFTR inhibitors show promising effects in slowing the progression of polycystic kidney disease (PKD), the most common genetic disease of the kidneys, according to preliminary research reported in the July 2008 issue of the Journal of the American Society Nephrology.
Although much more study is needed, CFTR inhibitors could provide a useful new approach for the treatment of PKD. "The CFTR inhibitors could be the basis of a lifelong treatment to slow renal cyst growth and decline in renal function, prolonging dialysis-free patient survival," comments Dr. Alan S. Verkman of University of California, San Francisco, School of Medicine.
Patients with PKD develop cysts on the kidneys, which progressively increase in size and number. The kidneys become enlarged, eventually leading to kidney failure. Previous research has suggested that the buildup of fluid in the cysts is related to chloride secretion, which is affected by the CFTR (cystic fibrosis transmembrane conductance regulator) gene. The researchers used automated "high-throughput" screening techniques to identify CFTR inhibitors that might affect cyst growth.
These screening studies identified two classes of small-molecule CFTR inhibitors that slowed the growth of renal cysts. The best inhibitor of each class was identified and shown to reduce the number and growth of cysts by more than 80 percent.
The inhibitors were then tested in mice that had been genetically altered to produce a condition similar to PKD. Animals treated with CFTR inhibitors for up to seven days had significantly slower cyst expansion and kidney enlargement, and better preservation of kidney function. There was no evidence of harmful effects on kidney function.
PKD is an incurable condition for which new treatments are urgently needed. If effective medications to reduce the rate of fluid buildup in cysts could be developed, they might provide an entirely new approach to treatment to slowing the progression of the disease.
The results show that CFTR plays a role in the growth of renal cysts, and suggest that CFTR inhibitors have potential as treatments to reduce cyst growth in PKD. However, much more research will be needed to see if drugs based on the CFTR blockers will be useful in human PKD.
"The mouse model of PKD is not the real human disease for many reasons, such as the more rapid progression of disease in mice," says Dr. Verkman. "Clinical trials will be needed to determine the efficacy of these compounds in human PKD."
This research was supported through grants from the National Institutes of Health (NIH), Cystic Fibrosis Foundation, and Polycystic Kidney Disease Foundation.The study entitled, "Small Molecule CFTR Inhibitors Slow Cyst Growth in PKD" will be available online at beginning on Wednesday, April 2, 2008 and in print in the July issue of the Journal of the American Society of Nephrology (JASN).
The American Society of Nephrology (ASN) is a not-for-profit organization of 11,000 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN publishes the Journal of the American Society of Nephrology (JASN), the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP).


Paternal age effect
From Wikipedia, the free encyclopedia
Jump to: navigation, search
The paternal age effect describes the influence that a father's age has on the chances of conferring a genetic defect to his offspring. Generally, older men have a greater probability of fathering children with a genetic defect than younger men do.[citation needed] This is seen as likely due to genetic copying errors which may increase in number after repeated spermatogenesis cycles over a man's lifetime.
1 Disorders correlated with paternal age
2 See also
3 References
4 External links

[edit] Disorders correlated with paternal age
Achondroplasia (dwarfism); craniofacial disorders such as Apert syndrome and Crouzon Syndrome; mental retardation of unknown etiologies; autism; and 25% of schizophrenia cases are correlated with advanced paternal age.
Other disorders related to advanced paternal age are:
Wilms' tumor
Thanatophoric dysplasia
Retinitis pigmentosa
Osteogenesis imperfecta type IIA
Fibrodysplasia ossificans progressiva
Bilateral retinoblastoma
Multiple exostoses
Marfan Syndrome
Lesch-Nyhan syndrome
Pfeiffer Syndrome
Wardenburg Syndrome
Treacher-Collins Syndrome
Soto’s basal cell nevus
Cleidocranial dysostosis
Polyposis coli
Oculodentodigital syndrome
Costello syndrome
Recklinghausen’s neurofibromatosis
Tuberous sclerosis
Polycystic kidney disease
Hemophilia A
Duchenne muscular dystrophy
Athetoid Cerebral Palsy
Dystonic Cerebral Palsy
Congenital Hemiplegia

[edit] See also
Maternal age effect

[edit] References
Crow JF (1997). "The high spontaneous mutation rate: Is it a health risk?". PNAS 94: 8380–6.
Bertram L, Busch R, Spiegl M, Lautenschlager NT, Müller U, Kurz A (1998). "Paternal age is a risk factor for Alzheimer disease in the absence of a major gene". Neuroscience 1 (4): 277–80.
Sipos A, Rasmussen F, Harrison G, Tynelius P, Lewis G, Leon DA, Gunnell D (2004). "Paternal age and schizophrenia: a population based (sic) cohort study". BMJ Online.
DNA repair activity linked to paternal age effect. University of Texas Health Science Center at San Antonio (2000-08-28).
Bray I, Gunnell D, Smith GD (2006). "Advanced paternal age: How old is too old?". Journal of Epidemiology and Community Health 60: 851–3.
Montgomery SM, Lambe M, Tomas O, Ekbom A (2004). "Paternal age, family size, and risk of multiple sclerosis". Epidemiology 15 (6): 717–23.
Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, Rabinowitz J, Shulman C, Malaspina D, Lubin G, Knobler HY, Davidson M, Susser E (2006). "Advancing paternal age and autism". Archives of General Psychiatry 63 (9): 1026–32.
Sanders L (2005). College scientist named Ellison Senior Scholar. University of Southern California College of Letters, Arts & Sciences.
Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA, Liberson GL (2003). "The influence of paternal age on down syndrome (sic)". J Urol 169 (6): 2275–8. PMID 12771769.
Rami B, Schneider U, Imhof A, Waldhör T, Schober E (1999). "Risk factors for type I diabetes mellitus in children in Austria" 158 (5): 362–6. PMID 10333115.
Singh NP, Muller CH, Berger RE (2003). "Effects of age on DNA double-strand breaks and apoptosis in human sperm". Fertility and sterility 80 (6): 1420–30.
Lauritsen MB, Pedersen CB, Mortensen PB (2005). "Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study". J Child Psychol Psychiatry 46 (9): 963–71. PMID 16108999.
Wohl M, Gorwood P (2007). "Paternal ages below or above 35 years old are associated with a different risk of schizophrenia in the offspring". Eur Psychiatry 22 (1): 22–6. PMID 17142012.
Schizophrenia Research Forum: Current Hypotheses (2006-03-28).
Choi J-Y, Lee K-M, Park SK, Noh D-Y, Ahn S-H, Yoo K-Y, Kang D (2005). "Association of paternal age at birth and the risk of breast cancer in offspring: a case control study". BMC Cancer 5: 143.
NW Andrology & Cryobank.
Croen LA, Najjar DV, Fireman B, Grether JK (2007). "Maternal and paternal age and risk of autism spectrum disorders". Archives of Pediatrics and Adolescent Medicine 161 (4): 334–40.
Tarin JJ, Brines J, Cano A (1998). "Long-term effects of delayed parenthood". Human Reproduction 13 (9): 2371–6.

[edit] External links

Labels: ,


Post a Comment

Subscribe to Post Comments [Atom]

<< Home