Alzheimer disease is characterized by adult-onset progressive dementia and typically begins with subtle memory failure that becomes more severe and eventually incapacitating. Other common symptoms include confusion, poor judgment, language disturbance, agitation, withdrawal, hallucinations, seizures, Parkinsonian features, increased muscle tone, incontinence, and mutism. About 5-6 per cent of sufferers of this debilitating mental wasting disease develop EOAD in middle age, thus it is known as a late-onset condition even though this particular rare form is early-onset by comparison. Of these cases, about 60 per cent, equivalent to 25,000 patients in Britain, are genetic.
In the couple we hope to treat, the man has a family history of EOAD with a number of affected relatives who all died from the condition in their 40s. Their aim is to select embryos free from the mutant gene predisposing the children to the condition, in an attempt to rid their family of the tragedy of Alzheimer's. If he carries the mutation, the condition is dominant and 50 per cent of his children are likely to be affected.
From the clinic's perspective, the PGD process will involve an application to the Human Fertilisation and Embryology Authority (HFEA) for a licence to perform the treatment in Britain after first ensuring that appropriate genetic markers are available to use in a single cell test. The case is further complicated by the fact that the couple wish to screen their embryos using a process known as 'exclusion' testing. This involves analysis of carefully selected genetic markers based on the man's family history allowing 'unaffected embryos' to be definitively selected without revealing the presence or absence of the mutation in the man himself. In this way, he can continue his life normally without any specific knowledge regarding his own genetic status with respect to EOAD.
The prospect of a successful licence application is high since one condition (of a growing number) already screened at our clinic includes Huntington's disease. This is quite similar to EOAD in that it represents another late-onset condition for which 'exclusion' testing has also been licensed.
Why not perform PGD for all Alzheimer's cases? The simple answer is that it would difficult to screen embryos for genes that predispose to late-onset Alzheimer's at present, because a number of different genes are involved and the presence of a mutation does not always result in disease. Furthermore, a disease that may not become apparent until person reaches their seventies or eighties (approaching normal life expectancy in the UK at present) is not a compelling candidate for PGD. However, EOAD affects patients in their forties and fifties (just exceeding the halfway point for life expectancy projections for 2031 according to the UK's Office of National Statistics (1) and, in specific families a single causative mutation is known and highly penetrant (meaning that inheritance of the mutation virtually guarantees the disease). Together, these facts make PGD a realistic way to prevent the disease in such families, rather than having only half a life worth living.
Following the recent report of this family's decision to choose PGD, Dr David King, Director of Human Genetics Alert, was sympathetic but opined: 'We can confidently expect science to find a cure for Alzheimer's in the next 40 years'. We welcome the prospect of cures for currently incurable diseases such as Alzheimer's. Whether or not his confidence is justified may be irrelevant for this couple who simply wish to remove the genetic problem from their family. Perhaps they don't wish to take the risk that there won't be a cure.
In addition, Dr King resurrects the philosophical position with respect to PGD that it is rarely better to have not been born at all. Many would agree that the choice between never being born and having 45 healthy years is a no-brainer both practically and philosophically speaking. Unfortunately, this thesis is simply a philosophical position. The real-life situation is very different. The couples actually face a more sophisticated array of options. Not only can they choose between childlessness and the risk of having a child with a significant chance of developing Alzheimer's as they themselves grow older and less able to provide support for the middle-aged 'child', PGD allows them select from a cohort of eight-cell embryos those free from the disease that has blighted several generations of their family.
Within the framework of PGD, the public considers the severity of genetic disease as subjective and opinions vary widely (2). Perception of the severity of a condition should properly be the domain of the primary care providers (that is, the parents). Furthermore, the HFEA Ethics and Law Committee concludes that diseases that are treatable and later-onset may still be considered 'serious' genetic conditions. In any case, the fact that a condition is treatable does not necessarily preclude PGD. Being ill and the vast physical, emotional and financial resources required to support those who suffer should not simply be ignored by individuals considering PGD.
PGD is all about choice for individual patients at risk of transmitting genetic disease to help prevent suffering for their families. PGD is not about discrimination against people with genetic disease, cancer or disabilities. Neither should PGD be viewed as diverting resources away from or removing the need for research into developing cures for genetic disease. The goal of PGD is to prevent the disease...not the cure.